Early-life lead exposure recapitulates the selective loss of parvalbumin-positive GABAergic interneurons and subcortical dopamine system hyperactivity present in schizophrenia.

Environmental factors have been associated with psychiatric disorders and recent epidemiological studies suggest an association between prenatal lead (Pb(2+)) exposure and schizophrenia (SZ). Pb(2+) is a potent antagonist of the N-methyl-D-aspartate receptor (NMDAR) and converging evidence indicates that NMDAR hypofunction has a key role in the pathophysiology of SZ. The glutamatergic hypothesis of SZ posits that NMDAR hypofunction results in the loss of parvalbumin (PV)-positive GABAergic interneurons (PVGI) in the brain. Loss of PVGI inhibitory control to pyramidal cells alters the excitatory drive to midbrain dopamine neurons increasing subcortical dopaminergic activity. We hypothesized that if Pb(2+) exposure in early life is an environmental risk factor for SZ, it should recapitulate the loss of PVGI and reproduce subcortical dopaminergic hyperactivity. We report that on postnatal day 50 (PN50), adolescence rats chronically exposed to Pb(2+) from gestation through adolescence exhibit loss of PVGI in SZ-relevant brain regions. PV and glutamic acid decarboxylase 67 kDa (GAD67) protein were significantly decreased in Pb(2+) exposed rats with no apparent change in calretinin or calbindin protein levels suggesting a selective effect on the PV phenotype of GABAergic interneurons. We also show that Pb(2+) animals exhibit a heightened locomotor response to cocaine and express significantly higher levels of dopamine metabolites and D2-dopamine receptors relative to controls indicative of subcortical dopaminergic hyperactivity. Our results show that developmental Pb(2+) exposure reproduces specific neuropathology and functional dopamine system changes present in SZ. We propose that exposure to environmental toxins that produce NMDAR hypofunction during critical periods of brain development may contribute significantly to the etiology of mental disorders.

The effect of individualized homeopathic treatment on the semen quality of bulls with reproductive disorders: a case series.

BACKGROUND: Poor semen quality of pedigree bulls has major economic implications in cattle breeding. AIMS: To evaluate the effect of homeopathy on the semen of bulls with reproductive disorders. METHODS: The behavioral, clinical and spermatic characteristics of four Nelore bulls were evaluated. The bulls received individualized homeopathic treatment mixed into the feed and administered once per day. Semen was collected using an artificial vagina. Successful collection, freezing, effective doses, and the number of doses of semen per collection were compared before and after homeopathic treatment. RESULTS: The bulls were treated with Sulphur, Phosphorus, Lycopodium and Argentum nitricum all in 30CH dilution. The rates of successful collection were 97.14%, 100%, 96.67% and 30.77% pretreatment and 95.45%, 100%, 94.67% and 96.77% at post-treatment for bulls A, B, C and D, respectively. The average number of doses per ejaculate pre and post-treatment were 102.67 (SD 74.41) vs. 300.08 (SD 180.58), 0 vs. 234.78 (SD 96.12), 0 vs. 105.12 (SD 54.98), 0 ± vs. 107.37 (SD 52.12) respectively. Many of these differences were statistically significant. CONCLUSION: The use of homeopathy apparently improved the production of viable doses of semen from bulls with previous freezing problems and poor semen quality. Controlled studies should be conducted.