Ti-Fei Yuan

Autologous neural stem cell transplantation: A new treatment option for Parkinson's disease?

The clinical motor dysfunction in Parkinson s disease (PD) is primarily linked to the depletion of dopamine in the striatum consecutive to the loss of the large dopaminergic neurons in the substantia nigra. Despite intense investigations, no effective therapy is available to prevent the onset, or to halt the progression of the neuronal cell loss. Here, we hypothesize that autologous adult neural stem cells (NSCs) are an attractive source for cell therapy to treat PD. They overcome the ethical issues inherent to the use of human fetal tissue or embryonic stem cells. NSCs derived from adult tissue also open the possibility for autologous transplantation, where NSCs are taken out from the patient, expanded and differentiated in vitro and re-implanted back as dopaminergic precursor cells.

Mirror neuron system based therapy for emotional disorders

Mirror neuron system (MNS) represents one of the most important discoveries in the area of neuropsychology of past decades. More than 500 papers have been published in this area (PubMed), and the major functions of MNS include action understanding, imitation, empathy, all of which are critical for an individual to be social. Recent studies suggested that MNS can modulate emotion states possibly through the empathy mechanism. Here we propose that MNS-based therapies provide a non-invasive approach in treatments to emotional disorders that were observed in autism patients, post-stroke patients with depression as well as other mood dysregulation conditions.

Einstein’s brain: Gliogenesis in autism?

The hypothesis is that the increased glia/neuron ratio in cortical areas of Einsteins brain is the sign of autism disorder rather than the evidence that more glial cells make a genius.

A broken BDNF hypothesis

(1) The hyperactivity hypothesis of BDNF in mania based on the observation that antidepressants that improve mood states can correspondingly upregulate BDNF levels in the brain, however, it has been proved that this is not the case for all antidepressants; for example, the SSRI antidepressant fluoxetine has either no effect [3] or decreases [4] BDNF mRNA in the rat hippocampus. (2) The hypoactivity hypothesis for BDNF in mania based on evidences from bipolar disorder patients, whose mood states include both mania and depression. Thus decreased BDNF levels should be attributed to an overall mood state evaluation rather mania states. (3) The BDNF hypothesis for mood requires reassessment. It has been found that infusion of BDNF into the hippocampus and raphenucleus region mimics behavioral effects of antidepressants, while infusion of BDNF into the ventral tegmental area (VTA) results in opposite effects [5]. This implies that BDNF might be a risk factor for mood disorder developments; however, the exact roles of BDNF under different conditions are determined by distinct pathways and neurotransmitters that involved in. (4) Genetically altered mice with disrupted BDNF functions lack spontaneous depressive phenotypes and evidences from single-nucleotide polymorphism are controversial [6]. The diverse regionally-specific rolesofBDNF inbrain permit itself to be amodulating factor on activity-dependent plasticity within emotional processing networks, the integrity of which will be compromised under mood disorders [7].

RNAi is less likely to be involved in the functions of venom.

Although Pereira and Lopes-Cendes gave us a very interesting hypothesis that RNAi mechanisms are involved in the toxic effects of venoms and poisons [1], we express some of cautious optimism about the theme. Firstly, the most distinguished characteristic of venom is the quick efficiency that hurts or even kills the victims, which is more likely to be achieved by blocking neurotransmission and interrupting the circular system in mammalians. The RNAi takes much longer time for dsRNA diffusion into important organs and silencing the gene expression, both of which are evolutionarily not economic. Second, as the authors have mentioned, a very simple physical RNAi antagonist is low temperature (26–30 C), both in plants [2] and mammalians [3], which reversely restricts the venomous species to be effectively in attacking preys or defending predators. Many venomous species are living in cold circumstances, though there’s still some possibility that dsRNAs were preserved as inactive forms. Additionally, many types of venom have either high or low pH, which further weakens the function of dsRNA. Collectively, we consider venoms are the secondary metabolites that are conserved during natural selections, the process of which is quite different with RNAi evolution. Thus RNAi approach is less likely to be recruited during the evolution of ‘‘toxin’’ families, though they may raise similar syndromes on general functions of the body.