Hippocampus postmortem

Anandamide is found in human brain 100 pmol/g in the hippocampus, 75 pmol/g in the thalamus, 60 pmol/g in the cerebellum, and 55 pmol/g in the striatum (Martin, 1999). The concentration of AEA increases postmortem, especially when the brain is kept at ambient temperature. Furthermore, AEA surges are observed when cerebellar granule cells are treated in hypoxic conditions (Hillard, 1997). Although such concentration increases may be artifacts of postmortem brain damage, they may also occur in living tissue under certain conditions, such as hypoxia. 

To date, little postmortem work has been done in human cannabis abusers. Preclinical studies indicate that chronic treatment with 5 -THC markedly reduces CBj receptor binding in all brain areas containing this receptor (cerebellum, hippocampus, cortex, globus pal-lidus, striatum), and enhances the cAMP pathway (Rubino et ah, 2000). Other preclinical work has shown that the cannabinoid receptor reserve is larger than that for most other G protein-coupled receptor systems (Gifford et ah, 1999). This means that at occupancies as low as 0.13%, 50% of maximal inhibition of Ach release is achieved. 

Szot P, White SS, Greenup JL, Leverenz JB, Peskind ER, Raskind MA (2006) Compensatory changes in the noradrenergic nervous system in the locus ceruleus and hippocampus of postmortem subjects with Alzheimer s disease and dementia with Lewy bodies. J. Neurosci. 26 467-478. 

The brain of AD patients is also characterized by the degeneration of basal forebrain cholinergic neurons, which innervates central regions involved in cognitive functions such as the cortex amygdala and hippocampus (1,3). The decline of cortical cholinergic activity as measured in postmortem brains... 

Adams CE, DeMasters BK, Freedman R. 1995. Regional zinc staining in postmortem hippocampus from schizophrenic patients. Schizophr Res 18 71-77. 

Several studies have consistently implicated SNAP-25 in schizophrenia. Postmortem SNAP-25 protein was found to be decreased in the hippocampus (Young et al., 1998 Fatemi et al., 2001 Thompson et al., 2003a), prefrontal cortex (Thompson et al., 1998 Karson et al., 1999), temporal cortex (Thompson et al., 1998), anterior frontal cortex (Honer et al., 2002), and cerebellum (Mukaetova-Ladinska et al., 2002) of individuals with schizophrenia. Conversely, elevated SNAP-25 in cerebrospinal fluid of patients with schizophrenia was observed (Thompson et al., 1999 Thompson et al., 2003b). One study failed to find a change in SNAP-25 in the prefrontal cortex (Brodman s area 9) of individuals with schizophrenia, but did find an increase in individuals with bipolar disorder (Scarr et al., 2006). 

The initial evidence for abnormalities of the hippocampus in schizophrenia came from postmortem and structural imaging studies. A study exploring volume changes in limbic brain regions reported... 

Cortex Postmortem studies have, in addition to striatal expression, also focused on DA receptor expression in frontal and temporal cortices, with a few studies in the hippocampus and the thalamus ( Table 4.2-1). In cortex, abnormalities of transcript expression for D1( D2, and D5 have not been found in schizophrenia (Roberts et al., 1994 Meador-Woodruff et al., 1997). Two studies have found a decreased cortical expression of the D3 receptor transcript (Schmauss et al., 1993 Meador-Woodruff et al., 1997), while postmortem D4 receptor transcript expression was reported either decreased (Meador-Woodruff et al., 1997), increased (Stefanis et al., 1998), or unchanged (Mulcrone and Kerwin, 1996 Roberts et al., 1996). 

Thalamus, Hippocampus Few postmortem studies have focused on the expression of DA receptors in the thalamus and hippocampal formation (O Table 4.2-1). One study reported a decreased number of cells positive for Dj transcripts in the CA3 hippocampal subfield, but with no change in I),... 

Consistent with changes observed in cortex, studies of mAChRs in the striatum and the hippocampus have found a decreased binding to M1/M4 ([3H]pirenzepine) and M2/M4 ([3H]AF-DX384) type receptors in postmortem tissue ( Table 4.2-7) (Dean et al., 1996 Crook et al., 1999 Crook et al., 2000 Scarr et al., 2007). However, the expression of transcripts for the Ml and M4 receptors was not altered. Binding to mAChRs has not been determined in the thalamus. 

Squires RF, Lajtha A, Saederup E, Palkovits M. 1993. Reduced [3H]flunitrazepam binding in cingulate cortex and hippocampus of postmortem schizophrenic brains Is selective loss of glutamatergic neurons associated with major psychoses Neurochem Res 18 219-223. 

The most researched area of interest for antidepressant activity related to signaling pathways is the hippocampus (79-85). The volume of the hippocampus is reduced in patients with multiple episodes of major depression, as observed in imaging studies and in postmortem samples (81-84). Animal models of inescapable stress are associated with decreased hippocampal neurogenesis (84). Neurogenesis is also evident in the hippocampus of humans (85). The neurogenesis hypothesis of depression states that depression is a consequence of impaired... 

Stockmeier CA, Mahajan GJ, Konick LC, Overholser JC, Juijus GJ, Meltzer HY, Uylings HBM, Ereidman L, Rajkowska G. Cellular changes in postmortem hippocampus in major depression. Biol. Psychiat. 2004 56 640-650. 

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