In this review, the most important neuropathological changes found in the cerebella of sheep affected by classical natural scrapie are discussed. This disease is the oldest known of a group of unconventional “infections” caused by toxic prions of different origins. Scrapie is currently considered a “transmissible spongiform encephalopathy” (due to its neuropathological characteristics and its transmission), which is the paradigm of prion pathologies as well as many encephalopathies (prion-like) that present aberrant deposits of insoluble protein with neurotoxic effects due to errors in their catabolization (“misfolding protein diseases”). The study of this disease is, therefore, of great relevance. Our work data from the authors’ previous publications as well as other research in the field. The four most important types of neuropathological changes are neuron abnormalities and loss, neurogliosis, tissue vacuolization (spongiosis) and pathological or abnormal prion protein (PrP) deposits/deposition. These findings were analyzed and compared to other neuropathologies. Various aspects related to the presentation and progression of the disease, the involution of different neuronal types, the neuroglial responses and the appearance of abnormal PrP deposits are discussed. The most important points of controversy in scrapie neuropathology are presented.
Treatment with second-generation antipsychotics (SGAs) can cause obesity and other cardiometabolic disorders linked to D2 receptor (DRD2) and to genotypes affecting dopaminergic (DA) activity, within reward circuits. We explored the relationship of cardiometabolic alterations with single genetic polymorphisms DRD2 rs1799732 (NG_008841.1:g.4750dup -> C), DRD2 rs6277 (NG_008841.1:g.67543C>T), COMT rs4680 (NG_011526.1:g.27009G>A), and VNTR in both DRD4 NC_000011.10 (637269-640706) and DAT1 NC_000005.10 (1392794-1445440), as well as with a multilocus genetic profile score (MLGP). A total of 285 psychiatric patients treated with SGAs for at least three months were selected. Cardiometabolic parameters were classified according to ATP-III and WHO criteria. Blood samples were taken for routinely biochemical assays and PCR genotyping. Obesity (BMI, waist (W)), high diastolic blood pressure (DBP), and hypertriglyceridemia (HTG) were present in those genetic variants related to low dopaminergic activity: InsIns genotype in rs1799732 (BMI: OR: 2.91 [1.42–5.94]), DRD4-VNTR-L allele (W: OR: 1.73 [1.04–2.87]) and 9R9R variant in DAT1-VNTR (W: OR: 2.73 [1.16–6.40]; high DBP: OR: 3.33 [1.54–7.31]; HTG: OR: 4.38 [1.85–10.36]). A low MLGP score indicated a higher risk of suffering cardiometabolic disorders (BMI: OR: 1.23 [1.05–1.45]; W: OR: 1.18 [1.03–1.34]; high DBP: OR: 1.22 [1.06–1.41]; HTG: OR: 1.20 [1.04–1.39]). The MLGP score was more sensitive for detecting the risk of suffering these alterations. Low dopaminergic system function would contribute to increased obesity, BDP, and HTG following long-term SGA treatment.
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