Neuroimmunological Model of Traumatic Memory

NCT00396695 | Unknown

• 1 other identifier: HP 6-198 R
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Traumatic events may lead to strong emotional episodic memories common in Post- Traumatic Stress Disorder(PTSD). Intense affect may inhibit efficacy of glutamatergic neurotransmission in two particular areas of the limbic system that have been implicated in the processing of emotionally charged memories: the amygdala and the hippocampus(1,2). Dysfunction of glutamatergic neurotransmission is associated with disbalance of long-term potentiation (LTP) and long-term depression (LTD)- two underlying mechanisms that cooperate to achieve synaptic plasticity and its expressations- learning and memory(3). LTP- the long lasting enhancement of synaptic function includes changes in the amount of neurotransmitter glutamate released into a synapse, changes in the levels of key proteins in synapses, protein phosphorylation and changes the density of receptors on their synaptic membranes. LTD is the inverse of LTP, a long lasting reduction in synaptic transmission (4). Interactions among the different forms of plasticity underlie different forms of memories. Normally these mechanisms are balanced. In the current literature there is data that a class I major histocompatibility complex (MHC class I) molecules, known to be important for immune responses to antigen, are expressed also by neurons that undergo activity-dependence, long-term structural and synaptic modifications (5). The brain produces its own immune molecules, the proteins MHC class I and CD3-zeta (a component of receptors for MHC class I). In the immune system, the two proteins act as part of a lock and key system to recognize and get rid of the body's foreign invaders. The CD3-zeta polypeptide is component of the T cell antigen receptor (TCR) which contribute to its efficient cell surface expression and account for part of its transducing capability (6). In the brain, they may be part of a signaling system that recognizes and eliminates inappropriate neural connections. Expression of MHC class I is regulated by the naturally occurring electrical activity, and sensitive to both natural and pathological changes in the activity. Electrical activity of neurons drives to an establishment of the final pattern of connection. Changes in the strength of individual synapses such as potention and depression leads to stabilization and withdrawal, respectively, of the affected connections. There are data, that in mice with deficiency of MHC class I and CD3-zeta the LTP in the hippocampus is enhanced significantly and LTD is absent. Thus, MHC class I is crucial for translating activity into changes in synaptic strength and neuronal connectivity in vivo. He required for normal activity dependent potentiation, depression, removal of inappropriate connection and responding to injury in the CNS (6). Glutamate receptors play critical roles in LTP/LTD mechanisms. Some researchers consider that a key role in pathogenesis of PTSD is being played by excessive excitation of NMDA-receptors in limbic system structures (1). The existing data allows to assume, that equation of plasticity mechanisms depends on mutual relations between the MHC class I and glutamate receptors. T-cells, like neurons, express high levels of glutamate receptors that are identical to the brain glutamate receptors. Presence of ionotropic and metabotropic glutamate receptors in membranes of lymphocytes makes them sensitive to the same alarm molecules which operate neuronal activity. Glutamate by itself triggers several T-cell activation which differs quantitatively or qualitatively from that ones triggered by "classical' T-cell activators like antigens(7). There are data about influence of T cell receptor-CD3 complex- on the expression of T-cells glutamate receptors (8). It is possible, that the key roles in this function play CD3-zeta.

Conditions

Stress Disorders, Post-Traumatic

Keywords

PTSD, traumatic memory

Interventions

Blood test PROCEDURE

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• male and female between 18-60 years
• PTSD

You may not qualify if:

• any immune system disease

Sponsors & Collaborators

• Ziv Hospital: lead

Study Sites (1)

Sieff Government Hospital

Safed, 13110, Israel

RECRUITING

Related Publications (7)

• Heresco-Levy U, Kremer I, Javitt DC, Goichman R, Reshef A, Blanaru M, Cohen T. Pilot-controlled trial of D-cycloserine for the treatment of post-traumatic stress disorder. Int J Neuropsychopharmacol. 2002 Dec;5(4):301-7. doi: 10.1017/S1461145702003061.

  PMID: 12466030 BACKGROUND

• Bessel van der Kolk. Memory and the evolving psychobiology of post traumatic stress. 1994.

  BACKGROUND

• Bellone C, Luscher C. mGluRs induce a long-term depression in the ventral tegmental area that involves a switch of the subunit composition of AMPA receptors. Eur J Neurosci. 2005 Mar;21(5):1280-8. doi: 10.1111/j.1460-9568.2005.03979.x.

  PMID: 15813937 BACKGROUND

• Gaiarsa JL, Caillard O, Ben-Ari Y. Long-term plasticity at GABAergic and glycinergic synapses: mechanisms and functional significance. Trends Neurosci. 2002 Nov;25(11):564-70. doi: 10.1016/s0166-2236(02)02269-5.

  PMID: 12392931 BACKGROUND

• Boulanger LM. MHC class I in activity-dependent structural and functional plasticity. Neuron Glia Biol. 2004 Aug;1(3):283-9. doi: 10.1017/S1740925X05000128.

  PMID: 18185853 BACKGROUND

• Malissen M, Gillet A, Rocha B, Trucy J, Vivier E, Boyer C, Kontgen F, Brun N, Mazza G, Spanopoulou E, et al. T cell development in mice lacking the CD3-zeta/eta gene. EMBO J. 1993 Nov;12(11):4347-55. doi: 10.1002/j.1460-2075.1993.tb06119.x.

  PMID: 8223444 BACKGROUND

• 7. Mia Levite. Direct Bi-Directional Dialogues Between The Nervous System And The Immune System in health and disease. www.weizmann.ac.il/neuro 2006.

  BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Alexander Mizruchin, MD

  Sieff Government Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander Mizruchin, MD

CONTACT

+ 972 50 8434245

Igor Krasnov, Ph.D

CONTACT

+ 972 4 6828828; yehudit.h@ziv.health.gov.il

Study Design

• Study Type: observational
• Observational Model: DEFINED POPULATION
• Time Perspective: OTHER
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: November 6, 2006
• First Posted: November 7, 2006
• Study Start: October 1, 2006
• Study Completion: December 1, 2007
• Last Updated: November 7, 2006

Record last verified: 2006-11

Locations

IL (1)