Synaptic densities

Post synaptic density protein/Drosophila disc large tumor suppressor/zonula occuldens-1 protein... 

Everall IP, Heaton RK, Marcotte TD, EUis RJ, McCutchan JA, Atkinson JH, Grant I, Mallory M, Masliah E (1999) Cortical synaptic density is reduced in mild to moderate human immunodeficiency virus neurocognitive disorder. HNRC Group. HIV Neurobehavioral Research Center. Brain Pathol 9 209-217... 

NMDA and AMPA receptors are spread across the post-synaptic density (PSD), whereas metabotropic glutamate receptors (except mGluR7) are located along the periphery of the PSD (Fig. 15-2). NMDA receptors appear to be present at most or all glutamatergic synapses whereas the content of AMPA receptors is variable - from zero to about 50 receptors per PSD [33]. Some synapses are silent , meaning that activation of them does not elicit AMPA receptor currents when the plasma membrane is hyperpolarized and Mg2+ blocks NMDA receptors. Such silent synapses contain only NMDA receptors. However, AMPA receptors are recruited from the cytosol to the PSD to activate such silent synapses in LTP. 

Developmentally, thyroid hormones interact with sex hormones such that hypothyroidism prolongs the critical period for testosterone-induced defeminization (see below) [3] in contrast, the hyperthyroid state prematurely terminates the sensitivity to testosterone [3]. Undoubtedly, an important link in these and other effects is synapse formation. Hypothyroidism increases synaptic density, at least transiently [3]. Interesting parallels with synapse formation are reported for learning behavior in rats neonatal hypothyroidism impairs learning ability, whereas hyperthyroidism accelerates learning initially, followed by a decline later in life [3]. 

Akama, K. T. and McEwen, B. S. Estrogen stimulates post-synaptic density-95 rapid protein synthesis via the Akt/ protein kinase B pathway. /. Neurosci. 23 2333-2339,2003. 

K., Miyazawa, S., Endo, S., and Suzuki, T. A novel ubiquitin-specific protease, synUSP, is localized at the post-synaptic density and post-synaptic lipid raft, J Neurochem, 2003, 87, 665-75. 

Nonetheless, there is considerable cause for concern about the use of psychotropic medication in preschool-age children during a period of continued rapid neural maturation (including synaptic remodeling and construction). The cortical synaptic density reaches its maximum at the age of 3 years and is substantially modified by the pruning process during the next 7 years (Huttenlocher, 1990). At the same time, the cerebral metabolic rate peaks between 3 and 4 years of... 

Sun Y, Savanenin A, Reddy PH, Liu YF (2001) Polyglutamine-expanded huntingtin promotes sensitization of N-methyl-D- aspartate receptors via post-synaptic density 95. J Biol Chem 276 24713-24718. 

The investigation of DAT immunolabeling at the ultrastructural level (Nirenberg et al., 1997b) visualized the DAT in varicose and intervaricose segments of axons in both the NAc core and the shell, with an organization similar to that detected in the dorsal striatum. Symmetric synapses were seen in both the two main NAc subregions, but DAT-immunoreactive processes only rarely formed synaptic junctions. DAT was not detected over synaptic densities and was instead mostly distributed on the extrasynaptic portions of the plasma membranes, near appositions with somata, dendrites, dendritic spines and astrocytes. 

The pathological snbstratum of HIV dementia is referred to as HIV encephalitis (HIVE). HIVE is a disseminated multifocal process characterized by the presence of multinucle-ated giant cells of macrophage/microglial origin microglial nodules diffuse astrocytosis myelin pallor loss of synaptic density and neuronal cell loss, mainly in the hippocampus. 

The idenhfication of 374 different proteins in the purified post-synaptic density of central excitatory synapses by LC-MS-MS was reported [61]. 13 phosphorylated sites were detected at 8 proteins. They also determined the molar concentrahon and relative stoichiometries of various scaffold proteins in the post-synaptic density. 

Okamoto PM, Gamby C, Wells D, Fallon J, Vallee RB. 2001. Dynamin iso-form-specific interaction with the shank/ proSAP scaffolding proteins of the post-synaptic density and actin cytoskeleton. J. Biol. Chem. 276 48458-65... 

In contrast to the aforementioned cannabinoid neuroprotection, some studies have reported a neurotoxic effect of THC. Thus, morphological changes in the hippocampus, decreases in the mean volume, synaptic density and dendritic length of CA3 pyramidal neurons, and reduced neuronal density in rat hippocampus associated with chronic THC oral administration have been described (Scallet et al. 1987). However, others could not find any significanthistopathological alteration in the brains of rats and mice treated orally with very high doses of THC for 2 years (Chan et al. 1996). Likewise, direct intracranial administration of THC or WIN 55,212-2 to rats for 1 week did not induce neural cell apoptosis (Galve-Roperh et al. 2000). 

Failure of cerebral cortical synaptic elimination is an unlikely possibility based on the timing of this phenomenon in normally developing individuals. In these studies (Huttenlocker et al., 1979, 1982, 1997), the primary visual and auditory cortices have peak synaptic density at 8-12 months and 3 months, respectively, with the period of synaptic elimination extending up to 11-12 years of age. In the frontal association cortices peak synaptic density occurs later at 1-2 years or at 3 1/2 years, depending on location, with the period of synaptic elimination extending to 12-15 years. Thus, the period of most active brain growth corresponds most closely with... 

Huttenlocher PR (1979) Synaptic density in human frontal cortex - developmental changes and effects of aging. Brain Res 163 195-205. 

---