Neuronal density

Magnetic resonance spectroscopy studies of COS patients revealed decreases in the ratio of N-acetyl aspartate to creatine (a putative marker of neuronal density) in the frontal cortex (Thomas et ah, 1998) and hippocampus (Bertolino et ah, 1998). These results were similar in direction and extent to those seen in adult patients. 

A magnetic resonance spectroscopy (MRS) study examined correlates of repetitive violence in 13 mildly mentally retarded individuals and 14 controls (Critch-ley et al., 2000). Concentrations and ratios of N-acetyl aspartate (NAA) and creatine phosphocreatine (Cr-l-PCr) were assayed. The NAA and CR-I-CR concentrations reflect neuronal density and high-energy phosphate metabolism, respectively. Violent patients had lower prefrontal concentrations of NAA and Cr-l-PCr and a lower NAA/Cr-l-PCr ratio in the amyg-dalohippocampal complex than that in controls. Within the violent group, prefrontal NAA concentration correlated with aggression frequency. 

Selemon LD, Rajkowska G, Goldman-Rakic PS. 1995. Abnormally high neuronal density in the schizophrenic cortex. A morphometric analysis of prefrontal area 9 and occipital area 17. Arch Gen Psychiatry 52 805-818. 

Selemon LD, Rajkowska G, Goldman-Rakic PS. 1998. Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients Application of a three-dimensional, stereologic counting method. J Comp Neurol 392 402-412. 

Currently, there is a commonly expressed view that decreased cortical volume in schizophrenia is the result of a reduction of cortical neuropil, presumably due to an atrophy of neural dendrites and axons (e.g., (Selemon and Goldman-Rakic, 1999)). A direct prediction of this model is that neuron density should be increased in proportion to the decrease in cortical volume. While there is some evidence for increased density in the prefrontal cortex (Selemon et al., 1995, 2003), there are also a number of negative findings (Akbarian et al., 1995 Cotter et al., 2002 Cullen et al., 2006 Thune et al., 2001). In auditory areas, the available studies have not shown an altered neuron density, even with hemispheric comparisons (Beasley et al., 2005 Cotter et al., 2004 Smiley et al., 2002). An alternative hypothesis is that reduced cortical volume is accompanied by a loss of neuron number, but this issue remains to be addressed in the auditory cortex. In other brain areas, there is some evidence for decreased neuron number, although the differences are often subtle and statistically nonsignificant (Benes et al., 1986 Dorph-Petersen et al., 2007 Stark et al., 2004 Thune et al., 2001). Changes in total cell number in the cerebral cortex have been difficult to determine, because these measurements require a clearly identified reference volume. 

Chana G, Landau S, Beasley C, Everall IP, Cotter D. 2003. Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia Evidence for decreased neuronal somal size and increased neuronal density Biol Psychiatry 53(12) 1086-1098. 

Selemon LD, Rajkowska G, Goldman-Rakic PS. 1998. Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients Application of a three-dimensional stereologic counting method. J Comp Neurol 392 402-412. Shapleske J, Rossell SL, Simmons A, David AS, Woodruff PW. 2001. Are auditory hallucinations the consequence of abnormal cerebral lateralization A morphometric MRI study of the sylvian fissure and planum temporale. Biol Psychiatry 49(8) 685-693. 

Shenton ME, Kikinis R, Jolesz FA, Poliak SD, LeMay M, et al. 1992. Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. N Engl J Med 327(9) 604-612. Smiley JF, Dwork AJ, Hackett TA, Ilievski B, Mancevski B, et al. 2002. Hemispheric comparisons of neuron density and volume of the human primary auditory cortex. Society for Neuroscience Abstracts. 

Another line of research is focused on the neurobiological development of the human brain in relation to schizophrenia. It has been hypothesised that schizophrenia is due to abnormal neurodevelopment, which results in a static encephalopathy that usually becomes manifest in adolescence. This abnormal development leads to morphological deviations such as enlarged or reduced brain structures, a disrupted communication between different brain structures, alterations in neuron density or decreased neuron size, and abnormal neuronal... 

GSK-3P deficiency in genetically modified mice is embryonic lethal, supporting a potentially important function during embryonic development where GSK-3 affects the Wnt and NFkB signalhng pathways [7]. These findings also suggest that GSK-3a cannot compensate for the fimction of GSK-3, further supporting distinct functions for the two isoforms. Selective overexpression of GSK-3 in the central nervous system (CNS) causes a reduction in brain and spinal cord volume in conjunction with reduced dendritic mass in the spinal cord. The reduction in brain voliune is accompanied by an increased neuronal density, but no apparent loss of neurons [8]. 

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). 

Some of the changes in minicolumnar organization seen in Alzheimer s disease will probably due to normal aging, and in area 46 of the rhesus monkey, in which senile plaques are uncommon, Cruz et al. (2004) using a density map method found that there is no age-related reduction in total neuronal density or in microcolumn width, length or periodicity. However, they did found subtle changes that indicate some disorganization of the minicolumns with age. 

Casanova ME, Buxhoeveden DP, Switala AE, Roy E (2002) Neuronal density and architecture (Gray level index) in the brains of autistic patients. J Child Neurol 17 515-521. 

Neurons are lost in all dementias. Neuronal loss is more difficult to assess than other findings in most biopsy specimens. The assessment requires quantitation more suited to morphometry than to the interpretative eye, and there is anatomic variation in neuronal density. Neuronal loss causes gliosis, which is easier to appreciate than loss of neurons after staining. 

Adler, J.E. and Black, I.B. (1985) Sympathetic neuron density differentially regulates transmitter phenotypic expression in culture. Proc. Natl. Acad. Sci. USA 82 4296-4300. 

Adams, B, Sazgar, M, Osehobo, P, Van der Zee, CE, Diamond, J, Fahnestock, M, Racine, RJ (1997) Nerve growth factor accelerates seizure development, enhances mossy fiber sprouting, and attenuates seizure-induced decreases in neuronal density in the kindling model of epilepsy. J Neurosci, 17 5288-5296. 

In the cerebral hemispheres, there was little change in weight or cell number (as measured by the DNA content) but in the visual cortex area an increase in neuronal density was apparent in the granular band in the second pregnancy iodine-deficient newborns. Synaptic counts also were reduced in the visual cortex (Table 2). 

Experimental studies on the hippocampus suggest a special vulnerability to lead. Louis-Ferdinand (1978) administered 7.5mg/kg lead acetate via intraperitoneal injection daily from birth to postnatal day 10 and reported a decrease in thickness of the hippocampal cell layer. This deficit was especially evident in the dentate gyrus, in which the granular cell layer showed a lowered neuronal density and prominent nucleoli, and within the hippocampal formation, where the pyramidal cell layer exhibited reduction in thickness. Although this study did not state blood lead values, there was no... 

It is noteworthy that cortical implants based on mechanically adaptive materials composed of PVAc/CNCs have indeed been found to reduce inflammation when compared to rigid silicon-based reference implants. Nguyen et al. recently reported an in-depth histological evaluation of the neuroinflammatory response to PVAc/CNC implants in comparison to rigid PVAc-coated reference implants and found a significant attenuation of microglia activation accompanied by retention of a high neuron density around the mechanically compliant implants. ... 

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