Lithium Salts Adopted for Psychopharmacological Use as the Modulators of Protein Synthesis in the Brain: Analytical Review

Retrieval labilizes memory traces and these gates two protein synthesis-dependent processes in the brain: extinction, which inhibits further retrieval, and reconsolidation, which may enhance retrieval or change its content. Extinction may itself suffer reconsolidation. Interactions among these processes may be applied to treatments of fear memories, such as those underlying post-traumatic stress disorders.

Download Full-text

The Role of the Entorhinal Cortex in Extinction: Influences of Aging

Neural Plasticity ◽

10.1155/2008/595282 ◽

2008 ◽

Vol 2008 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Lia R. M. Bevilaqua ◽

Janine I. Rossato ◽

Juliana S. Bonini ◽

Jociane C. Myskiw ◽

Julia R. Clarke ◽

...

Keyword(s):

Protein Synthesis ◽

Entorhinal Cortex ◽

Amyloid Plaques ◽

Memory Formation ◽

Amygdaloid Nucleus ◽

Dependent Protein Kinase ◽

Dependent Protein ◽

Glutamate Nmda Receptors ◽

The Brain

The entorhinal cortex is perhaps the area of the brain in which neurofibrillary tangles and amyloid plaques are first detectable in old age with or without mild cognitive impairment, and very particularly in Alzheimer's disease. It plays a key role in memory formation, retrieval, and extinction, as part of circuits that include the hippocampus, the amygdaloid nucleus, and several regions of the neocortex, in particular of the prefrontal cortex. Lesions or biochemical impairments of the entorhinal cortex hinder extinction. Microinfusion experiments have shown that glutamate NMDA receptors, calcium and calmodulin-dependent protein kinase II, and protein synthesis in the entorhinal cortex are involved in and required for extinction. Aging also hinders extinction; it is possible that its effect may be in part mediated by the entorhinal cortex.

Download Full-text

The Role of DNA, RNA and Protein Synthesis in Sexual Differentiation of the Brain

Integrative Hypothalamic Activity - Progress in Brain Research ◽

10.1016/s0079-6123(08)61917-2 ◽

1974 ◽

pp. 349-362 ◽

Cited By ~ 7

Author(s):

D.F. Salaman

Keyword(s):

Protein Synthesis ◽

Sexual Differentiation ◽

Rna And Protein Synthesis ◽

The Brain

Download Full-text

Calpain-1 and Calpain-2 in the Brain: Dr. Jekill and Mr Hyde?

Current Neuropharmacology ◽

10.2174/1570159x17666190228112451 ◽

2019 ◽

Vol 17 (9) ◽

pp. 823-829 ◽

Cited By ~ 8

Author(s):

Michel Baudry

Keyword(s):

Protein Synthesis ◽

Signaling Pathways ◽

Local Protein Synthesis ◽

Cell Functions ◽

Anchoring Proteins ◽

Associated Proteins ◽

Calpain 2 ◽

The Brain ◽

Calpain System ◽

Local Protein

While the calpain system has now been discovered for over 50 years, there is still a paucity of information regarding the organization and functions of the signaling pathways regulated by these proteases, although calpains play critical roles in many cell functions. Moreover, calpain overactivation has been shown to be involved in numerous diseases. Among the 15 calpain isoforms identified, calpain-1 (aka µ-calpain) and calpain-2 (aka m-calpain) are ubiquitously distributed in most tissues and organs, including the brain. We have recently proposed that calpain-1 and calpain- 2 play opposite functions in the brain, with calpain-1 activation being required for triggering synaptic plasticity and neuroprotection (Dr. Jekill), and calpain-2 limiting the extent of plasticity and being neurodegenerative (Mr. Hyde). Calpain-mediated cleavage has been observed in cytoskeleton proteins, membrane-associated proteins, receptors/channels, scaffolding/anchoring proteins, and protein kinases and phosphatases. This review will focus on the signaling pathways related to local protein synthesis, cytoskeleton regulation and neuronal survival/death regulated by calpain-1 and calpain-2, in an attempt to explain the origin of the opposite functions of these 2 calpain isoforms. This will be followed by a discussion of the potential therapeutic applications of selective regulators of these 2 calpain isoforms.

Download Full-text

Neuronal Damage after Repeated 5 Minutes of Ischemia in the Gerbil is Preceded by Prolonged Impairment of Protein Metabolism

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1992.60 ◽

1992 ◽

Vol 12 (3) ◽

pp. 425-433 ◽

Cited By ~ 32

Author(s):

R. Widmann ◽

C. Weber ◽

P. Bonnekoh ◽

M. Schlenker ◽

K.-A. Hossmann

Keyword(s):

Protein Synthesis ◽

Cerebral Ischemia ◽

Neuronal Damage ◽

Neuronal Injury ◽

Brain Regions ◽

Synthesis Rate ◽

Protein Synthesis Rate ◽

Single Episode ◽

Inhibition Of Protein Synthesis ◽

The Brain

The effect of single or repeated episodes of cerebral ischemia on protein biosynthesis and neuronal injury was studied in halothane-anesthetized gerbils by autoradiography of [14C]leucine incorporation into brain proteins and light microscopy. For quantification of the protein synthesis rate, the steady-state precursor pool distribution space for labeled and unlabeled free leucine was determined by clamping the specific activity of [14C]leucine in plasma, and by measuring free tissue leucine in samples taken from various parts of the brain. Control values of protein synthesis were 14.6 ± 2.2, 5.8 ± 2.3, 14.2 ± 3.1, and 10.0 ± 3.8 nmol g−1 min−1 (means ± SD) in the frontal cortex, striatum, CA1 sector, and thalamus, respectively. Following a single episode of 5 or 15 min of ischemia, protein synthesis recovered to normal in all brain regions except the CA1 sector, where it returned to only 50% of control after 6 h and to less than 20% after 3 days of recirculation. After three episodes of 5 min of ischemia spaced at 1 h intervals, protein synthesis remained severely suppressed in all brain regions after both 6 h and 3 days of recirculation. Inhibition of protein synthesis after 6 h predicted histological injury after 3 days of recirculation. In animals submitted to a single episode of 5 or 15 min of ischemia, histological damage was restricted to the CA1 sector but injury occurred throughout the brain after three episodes of 5 min of ischemia. These observations demonstrate that persisting inhibition of protein synthesis following cerebral ischemia is an early manifestation of neuronal injury. Prevention of neuronal injury requires restoration of a normal protein synthesis rate.

Download Full-text