Synaptic plasticity in depression: Molecular, cellular and functional correlates

Fuente: 

Progress in Neuro-Psychopharmacology and Biological Psychiatry

22 December 2012

• Author: W.N. Marsden^,

• Highclere Court, Woking, Surrey, GU21 2QP, UK

---

Abstract

Synaptic plasticity confers environmental adaptability through modification of the connectivity between neurons and neuronal circuits. 

This is achieved through changes to synapse-associated signaling systems and supported by complementary changes to cellular morphology and metabolism within the tripartite synapse. 

Mounting evidence suggests region-specific changes to synaptic form and function occur as a result of chronic stress and in depression. 

The prefrontal cortex (PFC) and hippocampus represent the best studied regions where functional and structural findings are consistent with a deficit in long-term potentiation (LTP), and neuronal and glial growth at excitatory synapses. 

Correlating these changes may be those to glutamate receptors (AMPARs and NMDARs), growth factor signaling (BDNF-TrkB) and several signal transduction pathways (NOS-NO, cAMP-PKA, Ras-ERK, PI3K-Akt, GSK-3, mTOR and CREB). 

In contrast other brain regions such as the amygdala may feature a somewhat opposite synaptic pathology including reduced inhibitory tone. 

Deficits in synaptic plasticity may further correlate disrupted brain redox and bioenergetics in stress and depression. 

Moreover, at a functional level region-specific changes to synaptic plasticity in depression may relate to maladapted neurocircuitry and parallel reduced cognitive control over negative emotion.

"The Promise of Cell Regeneration"

On October 3, 2011, Bryan Pollard represented Hyperacusis Research at the Summit on Hearing Restoration at the New York Academy of Medicine. 
This Summit was sponsored by the Hearing Health Foundation (formerly Deafness Research Foundation). 
It brought together the leaders in the field of cell regeneration research to discuss what needs to be accomplished for therapy for cell regeneration in the ear to become a reality. 

While this Summit did not relate directly to issues with Hyperacusis, the Hearing Restoration Project is an important effort because hair cell damage is still a possible consideration in the etiology of Hyperacusis. 
Also Hyperacusis Research is working together to sponsor a future research project with the Hearing Health Foundation.

Panel Discussion

The event started out with a panel discussion lead by Dr. Jon Lapook of the CBS Evening News. The members of the panel were: Dr. Sujana Chandrasekhar from New York Otology, Dr. Ed Rubel from the University of Washington, Dr. Stefan Heller from Stanford University and Dr. Andy Groves from Baylor College of Medicine. An interesting perspective from the panel discussion was how much less the NIH funds hearing research compared to cancer and other significant health issues. That was an important insight into possibly why it is even more difficult to get funding for hyperacusis since it represents only a fraction of the population with ear issues. 

Dr. Lopook referenced a recent news story highlighting the growing risk of hearing loss for children. 
There was a good question about why there were not more news stories on hearing challenges. Dr. Lopook described the significant challenge of getting even one deeper story of 5 or 6 minutes into the evening news every few weeks. 
Dr. Chandrasekhar gave a good overview the basic clinical types of cases she works with. She supports efforts with veterans who have hearing damage from the battle field. Dr. Rubel described the historical work that was accomplished to discover that birds and reptiles re-grow hair cells after damage. This gives a great model to study to understand why mammals are different since no mammal can re-grow hair cells after damage. Dr Heller gave a short description of how various types of stem cells can be used as a basis to initiate new hair cell growth.
 Finally Dr. Groves described briefly how hair cells grow. Each of these researchers gave a much more detailed description in their presentation.

How We Hear

The first speaker was Dr. George Gates who is on the board of the Hearing Health Foundation. His presentation gave a good overview of the basic ear function including the inner ear and hair cell function. He described how the outer hair cells (OHC) work from feedback signals to amplify quiet sounds. I asked a follow-up question about what other function the OHC has and he responded by describing that the OHC does provide some function to dampen loud sounds.

Hair Cell Regeneration

Dr. Rubel's presentation gave more details on birds and reptiles amazing hair cell recovery and re-growth from damage. For example, birds re-grow their hair cells in 22 days. His session ended with a question on Tinnitus. Another question related to both Tinnitus and Hyperacusis where a member of the audience referenced work in Germany to use lower level laser treatments to improve the condition of Tinnitus and Hyperacusis patients. No one on the panel was familiar with the work.

Barriers to Hair Cell Regeneration

Dr. Andy Groves presented details on hair cell regeneration that were highly technical. It appears there is a gene (P27) which won't allow hair cells to divide once cells are older. A key element to overcome this issue relates to Notch Signaling where one cell gives signals to the cell next to it which prevent the cell from changing into a different type of cell. Suffice it to say that there are some serious barriers to be overcome.

Stem Cells and Inner Ear Cell Regeneration

Dr. Heller described how stem cells work. He reviewed the 3 types of stem cells which enables various methods to obtain the needed building blocks. He then described how the process works to move from a stem cell to grow a specific type of cell such as a hair cell. This was also very technical and while occasional media stories make this sound like it is ready for prime time for certain diseases there are still huge barriers to overcome.

Conclusion

The key take-away is that while barriers remain large, the team felt overall that a real pathway is possible in the next decade or two. The most important aspect that relates to hyperacusis is that this research work will continue to drive the need for more detailed understanding of every inner ear component down to the molecular level. Every new piece of knowledge gained may further advance possible models relating to hyperacusis as long as we are connected to the work. For example, a key issue with hyperacusis is getting solid evidence for whether or not hyperacusis patients have hair cell damage. Currently all methods to truly establish hair cell damage can only be done on a destroyed cochlea. In a follow-up discussion, Dr. Heller described that recent advances in optical tomography may soon enable this diagnostic tool to be able to view inside a live cochlea. That breakthrough would enable many in the study of the inner ear to gain much needed understanding for modeling the inner ear and help to finally answer the question for damage for hyperacusis patients.
fuente:  http://hyperacusisresearch.org

Exercise-induced hypotension in autonomic disorders

• David A. Low^{a, b},
• Antonio C.L. da Nóbrega^c,
• Christopher J. Mathias^{a, b, ,}

• ^a Autonomic and Neurovascular Medicine Unit, Department of Medicine, Division of Brain Sciences, Faculty of Medicine, Imperial College London at St Mary's Hospital, UK
• ^b Autonomic Unit, National Hospital for Neurology & Neurosurgery, Queen Square/Division of Clinical Neurology, Institute of Neurology, University College London, London, UK
• ^c Department of Physiology and Pharmacology & Post-Graduate Program in Cardiovascular Sciences, Fluminense Federal University, Niterói, RJ, Brazil

 Abstract

The autonomic nervous system closely integrates a range of vital processes, including, cardiovascular function. 

Physical activity, or exercise, requires a range of integrated autonomic and cardiovascular adjustments in order to maintain homeostasis. 

Pathological conditions that result in dysfunction of the autonomic nervous system, such as autonomic failure, can therefore jeopardize the control of blood pressure resulting in hypotension and have serious implications for health. 

Exercise induced hypotension, defined as a ≥ 10 mm Hg fall in systolic blood pressure during exercise, can be a significant symptom/event for autonomic failure, as well as other autonomic disorder, patients, including, Multiple System Atrophy and Spinal Cord Injury, and can reduce physical capacity, orthostatic tolerance, result in falls, complicate management and reduce quality of life. 

The likely mechanisms do not appear to be an altered cardiac output or active muscle vasodilation response to exercise, but rather, a lack of and/or a blunted increase in sympathetic nerve activity during exercise and/or excessive vasodilation in the splanchnic circulation.

The severity of exercise induced hypotension seems to be higher during dynamic relative to static exercise. 

The possible management strategies for exercise induced hypotension include both non-pharmacological, e.g., reducing risk factors, and pharmacological measures, such as sympathomimetics, but studies on other pharmacological agents are limited.

 

fuetne : Autonomic Neuroscience

Volume 171, Issues 1–2, 2 November 2012, Pages 66–78

EPFL and Harvard Seek to Uncover Details Behind Hearing Loss

Monday, October 22nd 2012

What actually causes hearing loss in humans? And what are the best therapeutic approaches to this problem? 

Modern medicine hasn't yet been able to provide doctors with the right answers in many cases, because there has been no way to observe the tissue of the inner ear, without destroying it.

This situation was the starting point for a team of scientists from EPFL's School of Engineering (STI) and Harvard Medical School. They have been presented recently at the Bertarelli Symposium at EPFL, and will also appear in the online and print version of the Journal Of Biomedical Optics. 

Observing without destroying
The team's new optical method is groundbreaking in that it provides extremely clear images of inner ear tissue without any need for fluorescent labeling of the cells with antibiotics, proteins and other fluorescent markers that are usually used to "color" the targeted cells. 

This represents an enormous advantage compared with the traditional microscopic methods considered in recent years, which require fluorochrome markers and are therefore impossible to use in clinical practice.

"The markers irreversibly damage the tissue, which skews the analyses," said Xin Yang, co-author of the article and a doctoral assistant in Demetri Psaltis's Optics Laboratory (LO) at EPFL.

As for Magnetic Resonance Imaging (MRI), its resolution is inadequate for observing deep tissue cells.

"MRIs can't get beyond 40 microns (a micron equals one thousandth of a millimeter) and the cells we're looking at are on the order of two microns," said Yang.

Autofluorescent cells
To overcome the various obstacles in their path, the team takes advantage of the autofluorescence of the cells in the cochlea.

Autofluorescence refers to a phenomenon where certain cells tend to remit light after absorbing it. 

This phenomenon makes it possible to do without external fluorescent markers. 

The principle is simple: a laser is aimed at a specific target, causing the absorption of the photons by the cells' molecules. 

This excites the electrons, and a photon is emitted in return. 

These photons are then analyzed, providing a high quality image.
"To achieve better penetration into the tissue and a higher resolution 3D image, we use a method called two-photon microscopy," said Yang. 

A new method for endoscopic exams?
To test their approach experimentally the team used two populations of mice. 

One of the two groups was exposed to sounds that caused permanent damage to the inner ears, while the second group experienced a normal environment. 

The mice in both groups were then put down and their cochleas were removed. 

The scientists used their laser method and compared the results they obtained from each group.

"Among subjects exposed to the sounds, we observed irregularities in the way the cells were aligned and even some missing cells," said Yang.

Fuente: http://www.healthyhearing.com/

Improvements in Sensorineural Hearing Loss After Cord Blood Transplant in Patients With Mucopolysaccharidosis

Authors

Victor Da Costa, MD; Gwendolyn O’Grady, PhD, MS; Laura Jackson, AuD; David Kaylie, MD, MS; Eileen Raynor, MD

Fuente de la imagen: http://annareula.blogspot.com.ar/2010_12_01_archive.html

ABSTRACT

Objective  To objectively determine changes in sensorineural hearing in children with mucopolysaccharidosis (MPS) by comparing audiological data before and after hematopoietic stem cell transplantation (HSCT).

Design  Retrospective medical chart analysis.
Setting  Tertiary referral hospital.
Patients  Thirty pediatric patients with the diagnosis of MPS who underwent HSCT and had audiological data before and after HSCT. Data were extracted from medical charts for patients seen at our institution from January 1, 1999, to December 1, 2009.

Main Outcomes Measures  Hearing was assessed using behavioral audiometry testing and auditory brainstem responses (ABR) before and after HSCT. Patient demographics, diagnosis, and age at HSCT were also evaluated.

Results  Thirty patients with MPS were included. Four (13%) had MPS type 3a, 2 (7%) had MPS type 2, and 24 (80%) had MPS type 1.

The average age at HSCT was 19 months (range, 5-44 months).

Hearing improvement was evaluated by audiogram (20 patients), ABR (8 patients), and qualitative measures (30 patients).

On average, patients did not show improvement on audiogram (P = .28; paired t test).

The ABR click threshold improved 19 dB on average (P < .001). Qualitatively, 3 patients had normal hearing before and after HSCT. Of the remaining 27 patients, 20 (67%) showed improvement in sensorineural hearing (P < .001).

Five (17%) had hearing loss and did not improve.

Two (7%) had worsening hearing.

Hematopoietic stem cell transplantation at the age of 25 months or younger was significantly correlated with hearing improvement (P = .03).

Conclusions  Hematopoietic stem cell transplantation may provide improvement in MPS-associated sensorineural hearing loss.

Hearing improvement is more likely to occur in patients who undergo transplantation at 25 months or younger.

Fuente:  Arch Otolaryngol Head Neck Surg. 2012;138(11):1071-1076. 
doi:10.1001/jamaoto.2013.597.

Granddaughter's somersault treats cupulolithiasis of the horizontal semicircular canal

Authors

• Dirk Czesnik, MD^, ,
• David Liebetanz, MD

• Department of Clinical Neurophysiology, Medical School Göttingen, Georg-August-University of Göttingen, Robert-Koch-Str. 40, Göttingen, Germany

---

Abstract

We report on a 61-year-old woman with cupulolithiasis of the right horizontal semicircular canal, which is usually difficult to treat. 

The patient reported that several years ago, similar symptoms relieved completely after having performed several somersaults together with her granddaughter. 

This time, repetitive somersaults were again effective to treat her benign paroxysmal positional vertigo. 

Acceleration during a somersault may induce an intracanalicular force strong enough to detach otoconia debris from the cupula.

Rolling may then promote their reentrance into the utricle. This case suggests that repetitive somersaults may be an alternative treatment of cupulolithiasis of the horizontal semicircular canal.

Body rotation (A) and rotation of the horizontal semicircular canal during a somersault (B; lateral view). 
The gray line illustrates the position of horizontal semicircular canal. 
(C) The left picture illustrates how acceleration in the forward-facing direction during the somersault induce an intracanalicular force strong enough to detach otoconia debris from the cupula. 
The right picture demonstrates how ongoing rolling may move loose otoconia debris back into the utricle.

Fuente:

American Journal of Otolaryngology

Volume 34, Issue 1, January–February 2013, Pages 72–74

Progressive hearing loss following acquired cytomegalovirus infection in an immunocompromised child

---

Abstract

We report a rare case of progressive hearing loss after acquired CMV infection in a child with Langerhans cell histiocytosis (LCH).

 A 5-month-old female was diagnosed as having LCH. When she was 14 months old, she received an unrelated donor umbilical cord blood transfusion for the treatment of intractable LCH. 

CMV infection was confirmed after the blood transfusion. 

Because her own umbilical cord had no CMV, the CMV infection was not congenital. 

When she was 7 years old, mixed hearing loss was noted with bilateral otitis media with effusion. 

After that time, the sensorineural hearing loss progressed to bilateral profound hearing loss over 3 years. 

Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging with gadolinium contrast enhancement revealed a high intensity area in the inner ear that suggested bilateral labyrinthitis. 

  3D-FLAIR MRI after intervenous gadolinium administration. 

A was taken when she was 8 years old, and B was when she was 11 years old. 

The gadolinium enhancement of the internal auditory canal indicated by arrows was stronger in B than in A.

 This case demonstrates the possibility that, under the immunodeficiency, the acquired CMV infection causes progressive sensorineural hearing loss.

 Authors:

• Ken Kato, MD^{a, ,} ,
• Hironao Otake, MD, PhD^a,
• Mitsuhiko Tagaya, MD, PhD^a,
• Yoshiyuki Takahashi, MD, PhD^b,
• Yoshinori Ito, MD, PhD^b,
• Asahito Hama, MD, PhD^b,
• Hideki Muramatsu, MD, PhD^b,
• Seiji Kojima, MD, PhD^b,
• Shinji Naganawa, MD, PhD^c,
• Tsutomu Nakashima, MD, PhD^a

• ^a Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya, Japan
• ^b Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
• ^c Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

  

• fuente: American Journal of Otolaryngology.
  Volume 34, Issue 1, January–February 2013, Pages 89–92

tratamiento de urgencia del acúfeno

En el libro "el acúfeno como señal de malestar"
los autores

Miguel A. López González
Bioquímico
Otorrinolaringólogo
Hospital Universitario Virgen del Rocío
Sevilla
Francisco Esteban Ortega
Jefe de Servicio de Otorrinolaringología
Hospital Universitario Virgen del Rocío
Sevilla
Profesor Numerario de Otorrinolaringología
Universidad de Sevilla


nos señalan

Tratamiento de urgencia del acúfeno 

donde aparte de la medicación , resalto que los autores recomiendan terapia cognitiva-conductual,

 Ante cuadros de pacientes que solicitan asistencia de urgencia 
debido al síntoma acúfeno, se puede administrar medicación específica
junto con terapia conductual. 


Dexclorfeniramina

 
Una gragea de 6 mg como dosis inicial, continuando con 2 mg (un
comprimido) cada 8 horas hasta la disminución o desaparición del
acúfeno.
Alternativamente, una ampolla de 5 mg intramuscular, continuando
con 2 mg (un comprimido) cada 8 horas.

Sulpirida 

Un comprimido de 200 mg como dosis inicial, continuando con 50
mg (una cápsula) cada 8 horas hasta la disminución o desaparición
del malestar.
Alternativamente, una ampolla de 100 mg intramuscular,
continuando con 50 mg (una cápsula) cada 8 horas.

Diazepam 

 
Un comprimido de 25 mg como dosis inicial, continuando con 5 mg
(un comprimido) cada 8 horas hasta la disminución o desaparición
del malestar.
Alternativamente, una ampolla de 10 mg intramuscular como dosis
inicial, continuando con 5 mg (un comprimido) cada 8 horas.

Juntamente con la medicación, hay que realizar una terapia cognitiva-conductual que va a ser la que resuelva el caso definitivamente.

 Se investigarán los factores biopsicosociales incidentes para conseguir 
mediante los cambios pertinentes en la actitud o afrontamiento de los 
eventos, por parte del paciente, la superación o aceptación de sus 
circunstancias.  

Publicado por OTIN en 20:32
Fuente: Blog la puerta de la esperanza
 http://otinylucas.blogspot.com.ar/2012/12/tratamiento-de-urgencia-del-acufeno.html 

Recetas de cocina para los acúfenos. Arroz con delicias al tínnitus

Arroz con delicias al tínnitus

Ingredientes:

1. tres vasitos de arroz redondo, calidad extra. 

2. El mejor arroz el redondo, el de toda la vida
3. 6 vasitos de caldo vegetal
4. 1 zanahoria
5. 1 calabacín
6. 6 champiñones
7. jamon serrano en tacos pequeños
8. pimienta molida
9. aceite de oliva
10. sal

paciencia y buen hacer, tiempo 25 minutos, dificultad fácil
esta receta te aporta:

1. MELATONINA
2. ZINC
3. MAGNESIO
4. VITAMINA B3

alimentos excelentes para tratar el acúfeno, antioxidantes de la células ciliadas
Mientras cocinas esta receta, ponte en la casa música ambiental, suave, relajante para tratar tu hiperacusia.

Modo de hacer

En una sartén mediana, ponemos dos cucharaditas de aceite de oliva virgen extra, a fuego bajo.
Mientras tanto pelamos la zanahoria y la partimos muy fina, así como el calabacín también finamente picado, y los champiñones.
Añadimos la zanahoria y la dejamos pochar a fuego bajo-moderado, después de cinco minutos se añade el calabacin, y cuando pase un ratito añades por ultimo el champiñon y salpimentas al gusto.

Retiras en un plato las verduras fritas.

En la misma sarten añades el arroz que previamente habrás lavado en agua fría  lo rehogas en el aceite de las verduras a fuego moderado durante 3 minutos sin dejar de remover, pones el fuego a máxima potencia y añades los 6 vasitos de caldo, cuando empiece a hervir, lo bajas a fuego moderado-suave. El arroz redondo necesita 15 minutos para estar listo, cuando falten 5 minutos para terminar su cocción añades todas las verduras, y mezclas bien con el arroz.  Pasados los 15 minutos, apagas el fuego, y añades los taquitos de jamón (no antes pues se quedarían duros, al final de la receta recuerda), cubres con un paño de tela, mojado levemente con agua y dejas reposar 10 minutos.

Buen provecho

Bebida recomendadacerveza de trigo suave, ligera, afrutada

cava 

Publicado por OTIN en 18:39
Fuente:  http://otinylucas.blogspot.com.ar/2012/12/recetas-de-cocina-para-los-acufenos.html