Characterization of olfactory bulb glomeruli in schizophrenia.

Olfactory deficits, observed in schizophrenia, may be associated with a disruption of synaptic transmission in the olfactory system. Using immunohistochemistry and optical densitometry, we assessed the integrity of the synaptic connection between olfactory receptor neurons and olfactory bulb target neurons in schizophrenia by comparing the level of eight proteins, expressed in the olfactory bulb glomeruli, among schizophrenia and control subjects. In schizophrenia, no change was observed in the levels of OMP, GAP43 and NCAM, proteins expressed by olfactory receptor neurons, suggesting an intact innervation of the olfactory bulb by these neurons. This was supported by the absence of change in calbindin level, which has been shown to decrease after the destruction of the olfactory epithelium. The level of synaptophysin, a pre-synaptic protein, was also unchanged. These findings suggested that axons of olfactory receptor neurons establish synapses with their olfactory bulb targets in schizophrenia. The absence of change in the level of poorly phosphorylated neurofilament of moderate and high molecular weight (NFM/HP) suggested no lack of dendritic innervation despite a previously seen reduction of glomerular MAP2 level in schizophrenia subjects. This and above findings were consistent with the absence of change in the level of beta-tubulin III, a protein expressed by neurons of both olfactory epithelium and bulb. Finally, we noted no significant decrease in trkB level, a neurotrophin receptor involved in the olfactory epithelium maintenance. This study showed no evidence of major structural alteration of the synapse between the olfactory epithelium and bulb in schizophrenia.

The expression of retinoic acid receptor alpha is increased in the granule cells of the dentate gyrus in schizophrenia.

Mounting evidence suggests that schizophrenia is a neurodevelopmental disease resulting in dysfunctional connectivity between various brain regions. Retinoid pathway dysregulation has been proposed as a potentially important factor in the etiology of schizophrenia. Retinoid signaling plays a central role in many aspects of development, ranging from neurogenesis to activity-dependent plasticity, and regulates the expression of many candidate genes for schizophrenia. The retinoid pathway acts through two families of nuclear receptors highly expressed in the hippocampus, the retinoic acid (RAR) and retinoid X (RXR) receptors, both existing in three different subtypes (alpha, beta and gamma) and several isoforms. The present study examines the expression of the retinoid receptors in the dentate gyrus of schizophrenia and nonpsychiatric controls. The proportion of granule cells of the dentate gyrus expressing RAR(alpha) is increased by twofold in schizophrenia, while the proportion of cells expressing RAR(gamma)1 and 2, as well as RXR(beta) and gamma, is unchanged. These results demonstrate a dysregulation in the expression of at least one member of the RAR family of retinoid receptors in schizophrenia. Understanding the basis for this and how it affects downstream molecular pathways associated with hippocampal plasticity may provide insight into the dysfunctional connectivity of schizophrenia.

Exercise, sedentary pastimes, and cognitive performance in healthy older adults.

BACKGROUND: Moderately vigorous physical activity (MVPA) provides a protective affect against cognitive decline and cardiovascular risk factors. Less is known about sedentary pastimes or non exercise physical activity (NEPA) and cognitive performance. METHOD: 125 healthy adults 65 or older with no clinical evidence of cognitive impairment were enrolled. The CogState computerized neurocognitive battery was administered. Leisure activities were measured using the Community Health Activity Program for Seniors (CHAMPS). RESULTS: Sedentary pastimes were associated with executive dysfunction (P = 0.01); MVPA with high memory scores (P = 0.05) and NEPA with improved working memory (P = 0.05). Only sedentary pastimes and executive dysfunction retained significance after correction for multiple comparisons. Smoking and alcohol confounded the association of memory with sedentary pastimes and MVPA. CONCLUSIONS: Study highlights: negative impact of sedentary pastimes on executive function, need for additional investigation of sedentary behavior, NEPA, the impact of addictions upon activity in late life.

Microtubule-associated protein MAP2 expression in olfactory bulb in schizophrenia.

Previous studies have described alterations in presynaptic and postsynaptic elements in various parts of the CNS in schizophrenia, which may, at least in part, be due to abnormalities in neurodevelopmental processes. The olfactory bulb (OB) is a unique CNS area for examining synaptic development and plasticity in schizophrenia because it undergoes continuous reinnervation throughout life. Moreover, olfactory deficits and reduced OB volume have been observed in schizophrenia. We investigated the expression in the OB of the microtubule-associated protein MAP2, which has been shown to be abnormally expressed in the hippocampal region in schizophrenia. In both developing and mature neurons, MAP2 is an important structural component of dendrites and participates in the modification of synaptic organization. We used immunocytochemistry with phosphoepitope-specific and phosphorylation-state-independent antibodies to examine MAP2 expression in the glomerular layer of the OB in elderly subjects with chronic schizophrenia and controls. Phosphorylation-independent MAP2 expression was significantly reduced in schizophrenia, while phosphorylated MAP2 expression did not differ between groups. These results are consistent with faulty OB innervation in schizophrenia.