New learning and memory related pathways among the hippocampus, the amygdala and the ventromedial region of the striatum in rats.

BACKGROUND: The hippocampus, central amygdaloid nucleus and the ventromedial region (marginal division) of the striatum have been reported to be involved in the mechanism of learning and memory. This study aimed elucidating anatomical and functional connections among these brain areas during learning and memory. RESULTS: In the first part of this study, the c-Fos protein was used to explore functional connections among these structures. Chemical stimulation of either hippocampus or central amygdaloid nucleus results in dense expression of c-Fos protein in nuclei of neurons in the marginal division of the striatum, indicating that the hippocampus and the central amygdaloid nucleus might be functionally connected with the marginal division. In the second part of the study, the cholera toxin subunit B-horseradish peroxidase was injected into the central amygdaloid nucleus to observe anatomical connections among them. The retrogradely transported conjugated horseradish peroxidase was observed in neurons of both the marginal division and dorsal part of the hippocampus following the injection. Hence, neural fibers from both the marginal division and the hippocampus directly projected to the central amygdaloid nucleus. CONCLUSION: The results implicated potential new functional and structural pathways through these brain areas during the process of learning and memory. The pathways ran from ventromedial portion (the marginal division) of the striatum to the central amygdaloid nucleus and then to the hippocampus before going back to the marginal division of the striatum. Two smaller circuits were between the marginal division and the central amygdaloid nucleus, and between the central amygdaloid nucleus and the hippocampus. These connections have added new dimensions of neural networks of learning and memory, and might be involved in the pathogenesis of dementia and Alzheimer disease.

Enzymatically active Rho and Rac small-GTPases are involved in the establishment of the vacuolar membrane after Toxoplasma gondii invasion of host cells.

BACKGROUND: GTPases are the family of hydrolases that bind and hydrolyze guanosine triphosphate. The large Immunity-related GTPases and the small GTPase ADP-ribosylation factor-6 in host cells are known to accumulate on the parasitophorous vacuole membrane (PVM) of Toxoplasma gondii and play critical roles in this parasite infection, but these GTPases cannot explain the full extent of infection. RESULTS: In this research, RhoA and Rac1 GTPases from the host cell were found to accumulate on the PVM regardless of the virulence of the T. gondii strains after T. gondii invasion, and this accumulation was dependent on their GTPase activity. The real-time micrography of T. gondii tachyzoites invading COS-7 cells overexpressing CFP-RhoA showed that this GTPase was recruited to the PVM at the very beginning of the invasion through the host cell membrane or from the cytosol. Host cell RhoA and Rac1 were also activated after T. gondii tachyzoites invasion, which was needed for host cell cytoskeleton reorganization to facilitate intracellular pathogens invasion. The decisive domains for the RhoA accumulation on the PVM included the GTP/Mg2+ binding site, the mDia effector interaction site, the G1 box, the G2 box and the G5 box, respectively, which were related to the binding of GTP for enzymatic activity and mDia for the regulation of microtubules. The recruited CFP-RhoA on the PVM could not be activated by epithelial growth factor (EGF) and no translocation was observed, unlike the unassociated RhoA in the host cell cytosol that migrated to the cell membrane towards the EGF activation spot. This result supported the hypothesis that the recruited RhoA or Rac1 on the PVM were in the GTP-bound active form. Wild-type RhoA or Rac1 overexpressed cells had almost the same infection rates by T. gondii as the mock-treated cells, while RhoA-N19 or Rac1-N17 transfected cells and RhoA, Rac1 or RhoA + Rac1 siRNA-treated cells showed significantly diminished infection rates compared to mock cells. CONCLUSIONS: The accumulation of the RhoA and Rac1 on the PVM and the requisite of their normal GTPase activity for efficient invasion implied their involvement and function in T. gondii invasion.

[The impact of Toxoplasma gondii infection on host cell signal transduction].

In the process of invasion and development in host cells, Toxoplasma gondii causes acute and chronic infection. The parasite manipulates the host cell elaborately and integrated to keep a delicate balance between induction and elimination of the host cell immune reaction. It can then dwell and multiply successfully in the host cell, and hopefully be transmitted to a definitive host The host cell signaling is changed and regulated extensively by the parasite in the process, which plays vital roles in parasite invasion and development. This review shed light on the manipulation of host cell signaling by T. gondii infection in these aspects: (1) T. gondii secreted proteins which manipulate host cell signaling; (2) T. gondii modulates the innate and protective immune related host cell signaling; (3) T. gondii regulates anti-apoptotic reaction and cell cycle related host cell signaling; (4) T. gondii adjusts calcium relevant host cell signaling; (5) T. gondii manipulates cell structure reorganization relevant host cell signaling.