Cerebellar connections with the motor cortex and the arcuate premotor area: an analysis employing retrograde transneuronal transport of WGA-HRP

We have employed transneuronal transport to examine the anatomical relationships between the deep cerebellar nuclei and 2 cortical motor areas: the primary motor cortex and the arcuate premotor area (APA). In the same animals, we have also examined the patterns of labeling in the thalamus and the red nucleus to provide evidence for the potential routes of transneuronal transport to the cerebellum. When the appropriate technical procedures were employed, cortical injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) resulted in transneuronal labeling within portions of the contralateral deep cerebellar nuclei. Injections into the primary motor cortex labeled neurons in the dentate and in the 2 subdivisions of the interpositus. Injections into the APA labeled neurons in the dentate and in only the posterior subdivision of the interpositus. In most instances, dentate neurons were more intensely labeled following the cortical injections than interpositus neurons. The transneuronal labeling observed in the dentate nucleus was topographically organized. The dentate region that was labeled following injections into the "arm area" of the APA was caudal and ventral to the dentate region that was labeled following injections into the "arm area" of the primary motor cortex. This observation provides evidence for two "arm areas" in the dentate: one anatomically related to the APA, and the other related to the primary motor cortex. More than one route of transport may be responsible for the labeling of cerebellar neurons. We propose that the labeling observed in the dentate nucleus reflects the pattern of connections in the cerebellothalamocortical pathways that link the dentate with the cerebral cortex. Thus, our observations support the concept proposed by Schell and Strick (J. Neurosci. 4:539-560, '84)--that the cortical targets of the dentate nucleus include both the primary motor cortex and the APA.     

Effects of Hypericum extract on the acetylcholine release: a loose patch clamp approach.

The St. John's Wort (Hypericum perforatum) extract (Hp) represents one of the most useful natural therapeutic agents in the treatment of moderate and mild depression. The antidepressant effects of Hp are different, by a molecular mechanism point of view, when compared to those of other antidepressant drugs and, we think, a further pharmacological characterization is needed. It is suggested that the neurochemical effects of Hp could be bind either to its activity on the uptake of some mediators in the central nervous system or to the inhibition of some enzymatic activity at the receptor level. The present study carried out with the loose patch clamp (LPC) in the mouse neuromuscular junction, indicates a potentiation of the acetylcholine (ACh) action at the mouse neuromuscular junction. The spontaneous release of ACh was unaffected by Hp indicating that neither presynaptic nor postsynaptic function are modified by Hp. Indeed, both the frequency and the amplitude of the miniature end-plate currents (mepcs) were unmodified by Hp. Furthermore, the mepcs decay time (tau), i.e. the apparent cholinergic channel life time, was significantly increased after Hp treatment. The other parameter affected was the amplitude of the evoked end-plate currents (epcs) which was constantly and in a dose dependent manner increased by Hp. These findings suggest a possible action of Hp on the acetylcholinesterase (AChE) in terms of a reduction of the degradation rate of ACh.     

CTLA-4 exon 1 polymorphism in patients with autoimmune blood disorders

CTLA-4 is a CD28 homologue that plays an important role in negative regulation of T-cell responses. Its transient expression on the surface of activated T cells antagonizes the activating signals and terminates the T-cell response. An A to G polymorphism at position 49 of the CTLA-4 first exon has recently been associated with several autoimmune disorders. In the present study we have examined the prevalence of the A and G alleles of the CTLA-4 gene in 50 patients with autoimmune hemolytic anemia (AIHA), of which 20 had idiopathic AIHA and 30 had AIHA and chronic lymphocytic leukemia (CLL), and in 60 patients with immune thrombocytopenic purpura (ITP). Control subjects were 100 healthy individuals and 100 CLL patients without clinical evidence for an autoimmune disease. The G allele was present at a significantly higher frequency among the patients with AIHA (P = 0.003), whereas no difference was observed between patients with ITP and controls. The G allele frequency was highest among CLL patients who had developed AIHA. The obtained data indicate that the G allele of CTLA-4 predisposes to the development of AIHA, particularly among patients with CLL.