Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue i...

Brown Adipose Tissue: Function and Physiological Significance

https://deepblue.lib.umich.edu/bitstream/2027.42/28186/1/0000638.pdf

The functional anatomy of basal ganglia disorders.

The adolescent brain and age-related behavioral manifestations

There is an increasing amount of experimental evidence that oxidative stress is a causal, or at least an ancillary, factor in the neuropathology of several adult neurodegenerative disorders, as well as in stroke, trauma, and seizures. At the same time, excessive or persistent activation of glutamate-gated ion channels may cause neuronal degeneration in these same conditions. Glutamate and related acidic amino acids are thought to be the major excitatory neurotransmitters in brain and may be utilized by 40 percent of the synapses. Thus, two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain. The broad distribution in brain of the processes regulating oxidative stress and mediating glutamatergic neurotransmission may explain the wide range of disorders in which both have been implicated. Yet differential expression of components of the processes in particular neuronal systems may account for selective neurodegeneration in certain disorders.

https://science.sciencemag.org/content/sci/262/5134/689.full.pdf

Oxidative stress, glutamate, and neurodegenerative disorders

• Recent research on schizophrenia has demonstrated that in this disorder the brain is not, strictly speaking, normal. The findings suggest that nonspecific histopathology exists in the limbic system, diencephalon, and prefrontal cortex, that the pathology occurs early in development, and that the causative process is inactive long before the diagnosis is made. If these findings are valid and not epiphenomena, then the pathogenesis of schizophrenia does not appear to fit either traditional metabolic, posttraumatic, or neurodegenerative models of adult mental illness. The data are more consistent with a neurodevelopmental model in which a fixed "lesion" from early in life interacts with normal brain maturational events that occur much later. Based on neuro-ontological principles and insights from animal research about normal brain development, it is proposed that the appearance of diagnostic symptoms is linked to the normal maturation of brain areas affected by the early developmental pathology, particularly the dorsolateral prefrontal cortex. The course of the illness and the importance of stress may be related to normal maturational aspects of dopaminergic neural systems, particularly those innervating prefrontal cortex. Some implications for future research and treatment are considered.

Implications of normal brain development for the pathogenesis of schizophrenia

The regional distributions of iron, copper, zinc, magnesium, and calcium in parkinsonian brains were compared with those of matched controls. In mild Parkinson's disease (PD), there were no significant differences in the content of total iron between the two groups, whereas there was a significant increase in total iron and iron (III) in substantia nigra of severely affected patients. Although marked regional distributions of iron, magnesium, and calcium were present, there were no changes in magnesium, calcium, and copper in various brain areas of PD. The most notable finding was a shift in the iron (II)/iron (III) ratio in favor of iron (III) in substantia nigra and a significant increase in the iron (III)-binding, protein, ferritin. A significantly lower glutathione content was present in pooled samples of putamen, globus pallidus, substantia nigra, nucleus basalis of Meynert, amygdaloid nucleus, and frontal cortex of PD brains with severe damage to substantia nigra, whereas no significant changes were observed in clinicopathologically mild forms of PD. In all these regions, except the amygdaloid nucleus, ascorbic acid was not decreased. Reduced glutathione and the shift of the iron (II)/iron (III) ratio in favor of iron (III) suggest that these changes might contribute to pathophysiological processes underlying PD.

Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains.

Significant differences in the content of iron (III) and total iron were found in post mortem substantia nigra of Parkinson's disease There was an increase of 176% in the levels of total iron and 255% of iron (III) in the substantia nigra of the parkinsonian patients compared to age matched controls In the cortex (Brodmann area 21), hippocampus, putamen, and globus pallidus there was no significant difference in the levels of iron (III) and total iron Thus the changes in total iron, iron (III) and the iron (II)/iron (III) ratio in the parkinsonian substantia nigra are likely to be involved in the pathophysiology and treatment of this disorder

Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain.

A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia.

Brains of 49 patients who had died with Alzheimer's disease and 54 controls were examined. The Alzheimer group exhibited noticeably reduced activity of the cholinergic marker enzyme choline acetyltransferase in the cerebral cortex, but cortical concentrations of noradrenaline, gamma-aminobutyric acid, and somatostatin were also significantly reduced. Analysis of the results according to age at death showed that the older patients, dying in their 9th and 10th decades, had a relatively pure cholinergic deficit confined to temporal lobe and hippocampus, together with a reduced concentration of somatostatin confined to temporal cortex. By contrast, the younger patients, dying in their 7th and 8th decades, had a widespread and severe cholinergic deficit together with the abnormalities of noradrenaline, gamma-aminobutyric acid, and somatostatin, and the younger patients accounted for most of the abnormalities in these systems observed in the overall group. Comparison of the young subjects with Alzheimer's disease with the older controls did not support the concept of Alzheimer's disease representing an acceleration of the aging process. These results suggest that Alzheimer's disease in people aged under 80 may represent a distinct form of presenile dementia which differs in important respects from the dementia of old age.

https://www.bmj.com/content/bmj/288/6422/961.full.pdf

Neurochemical characteristics of early and late onset types of Alzheimer's disease.

There is a growing body of evidence in support of the view of schizophrenia as a dysfunction of the left temporal lobe. This hypothesis, first proposed by Flor-Henry, stemmed from the frequently observed association of schizophreniform psychoses with left-sided temporal lobe epilepsy. As yet the evidence is solely clinical, with a wide range of psychological and physiological measurements indicating a left hemisphere disorder in patients with schizophrenia. It is not, however, inconsistent with the major neurochemical hypothesis of schizophrenia, which proposes an increase in dopaminergic neurotransmission which can be blocked by neuroleptic drugs. One region of the medial temporal lobe, the amygdala, receives a major dopaminergic innervation from the ventral tegmental area. In fact this meso-limbic dopaminergic tract, which also innervates the nucleus accumbens and olfactory tubercule, has been implicated in psychosis and in antipsychotic drug action. We have attempted here to test whether there is a neurochemical correlate of the Flor-Henry hypothesis using brain tissue collected post mortem from schizophrenic patients and controls. The results indicate that a specific increase of dopamine is found in the amygdalae in the left cerebral hemisphere of the schizophrenic group.

Gavin P. Reynolds

Papers

Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains.

Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain.

A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia.

Neurochemical characteristics of early and late onset types of Alzheimer's disease.

Increased concentrations and lateral asymmetry of amygdala dopamine in schizophrenia