Neuropathological changes in the nucleus basalis in schizophrenia

Abstract

The nucleus basalis has not been examined in detail in severe mental illness. Several studies have demonstrated decreases in glia and glial markers in the cerebral cortex in schizophrenia, familial bipolar disorder and recurrent depression. Changes in neocortical neuron size and shape have also been reported. The nucleus basalis is a collection of large cholinergic neurons in the basal forebrain receiving information from the midbrain and limbic system, projecting to the cortex and involved with attention, learning and memory, and receives regulation from serotonergic inputs. Forty-one cases aged 41-60 years with schizophrenia or major depressive disorder with age-matched controls were collected. Formalin-fixed paraffin-embedded coronal nucleus basalis sections were histologically stained for oligodendrocyte identification with cresyl-haematoxylin counterstain, for neuroarchitecture with differentiated cresyl violet stain and astrocytes were detected by glial fibrillary acid protein immunohistochemistry. Cell density and neuroarchitecture were measured using Image Pro Plus. There were larger NB oval neuron soma in the combined schizophrenia and major depression disorder groups (p = 0.038), with no significant change between controls and schizophrenia and major depression disorder separately. There is a significant reduction in oligodendrocyte density (p = 0.038) in the nucleus basalis in schizophrenia. The ratio of gemistocytic to fibrillary astrocytes showed a greater proportion of the former in schizophrenia (18.1 %) and major depressive disorder (39.9 %) than in controls (7.9 %). These results suggest glial cell abnormalities in the nucleus basalis in schizophrenia possibly leading to cortical-limbic disturbance and subcortical dysfunction.

Correlations between physical activity and neurocognitive domain functions in patients with schizophrenia: a cross-sectional study

“…Abnormality of the basal nucleus in schizophrenia has been reported [24]. Furthermore, anatomical differences in the basal nucleus between treatment-responsive and treatment-resistant patients have been reported in a recent systematic review [25].…”

The neurobiology of transition to psychosis

“…[42][43][44] First, postmortem studies have reported that significant reduction (14%-22%) in the density and the quantity of oligodendrocytes (cells producing myelin) [44][45][46][47][48][49][50][51][52][53][54][55][56] is seen alongside signs of apoptotic damage to myelin sheaths, 52,55,57 especially in the grey matter, and downregulation of myelin-related genes and proteins. [58][59][60][61][62][63][64] Arguably, of all the expressed brain proteins with recorded abnormalities, astrocytic and oligodendrocytic proteins appear to be the most consistently affected in patients with schizophrenia.…”

Basal forebrain mediated increase in brain CRF is associated with increased cholinergic tone and depression

“…For example, Williams et al (2013) collected 41 coronal blocks within the nucleus basalis of individuals, aged 41-60 years, diagnosed with either major depressive disorder (n=11, of which 7 died of suicide or asphyxiation), schizophrenia (n=13) or with age-matched controls (n=16). Examining cell density and neuroarchitecture, results indicated a larger nucleus basalis oval neuron soma in the combined clinical groups (p = 0.038), with no significant differences between controls and schizophrenia and major depression disorder separately.…”