39 research outputs found
Ultrastructural study of the neural microcircuits in the sensory epithelium of the paratympanic organ of the chicken.
No full textThe paratympanic organ (PTO) is a sensory organ located in the medial wall of the tympanic cavity of birds. The organ looks like a small tapering vesicle, and is equipped with a sensory epithelium formed by supporting cells (SCs) and Type II hair cells (Type II-HCs). The function of the PTO has not yet been precisely defined. The prevailing current hypothesis is that the PTO assesses the air pressure exerted on the external surface of the tympanic membrane. The PTO could may thus function as a barometer and, in flying birds, also as an altimeter. The afferent synapses of the PTO of chicken were described in detail in a previous paper. Reciprocal synapses between efferent nerve endings (ENEs) and the HCs were also observed, suggesting the existence of local microcircuits. The aim of this work was to provide a more detailed ultrastructural description of these microcircuits in the PTO of chicken. We observed for the first time: (1) reciprocal synapses between the HCs and the afferent nerve endings (ANEs); (2) presence of two distinct types of ENEs; (3) reciprocal synapses between the HCs and both types of ENEs. Overall, these results indicate that a complex processing of the incoming sensory signals may occur in the PTO. This thus suggests that the PTO may perform more complex functions than those supposed until now. We hypothesize that the PTO could have a role in the low-frequency sound perception
Connecting pre-clinical knowledge to modern imaging techniques in gross anatomy learning
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NOVEL INSIGHT ON THE FINE MECHANISMS OF THE ACTION OF METHAMPHETAMINE WITHIN CATECHOLAMINERGIC NEURONS
No full textMethamphetamine (METH) is abused worldwide and it represents a threaten for public health. METH exposure induces a variety of detrimental effects. In fact, METH produces a number of oxidative species, which lead to lipid peroxidation, protein misfolding and nuclear damage. Cell clearing pathways such as proteasome (UP) and autophagy (ATG) are involved in METH-induced oxidative damage. Although these pathways were traditionally considered to operate as separate metabolic systems, recent studies demonstrate their interconnection at functional and biochemical level. Very recently, the convergence between UP and ATG was evidenced within a single organelle named autophagoproteasome (APP), which is suppressed by mTOR activation. In the present research study, the occurrence of APP during METH toxicity was analyzed. In fact, co-immune-precipitation indicates a binding between LC3 and P20S particles, which also recruit p62 and alpha-synuclein. The amount of METH-induced toxicity correlates with APPs levels. Specific markers for ATG and UP, such as LC3 and P20S in the cytosol, and within METH-induced vacuoles, were measured at different doses and time intervals following METH administered either alone, or combined with mTOR modulators. Different approaches were used to document the effects of mTOR modulation on METH toxicity and the merging of UP with ATG markers within APPs. METH-induced cell death is prevented by mTOR inhibition while it is worsened by mTOR activation, which correlates with the amount of autophagoproteasomes. The present data, which apply to METH toxicity, are also relevant to provide a novel insight into cell clearing pathways to counteract several kind of oxidative damage
THE EFFECTS OF RAPAMYCIN ON THE OCCURRENCE OF PRIONOIDS IN GLIOBLASTOMA MULTIFORME
No full textRecently, increasing evidence indicates a role for cellular prion protein (PrPc) in fostering stemness and invasion of glioblas- toma multiforme (GBM). Besides being implicated in the patho- genesis and transmission of prion diseases, PrPc is emerging as a key in maintaining glioblastoma cancer stem cells (GSCs) phe- notype, thereby strongly affecting GBM infiltration and relapse. This might apply to other proteins, which share a prion-like struc- ture and biology. Thus, suppressing the expression of these pro- teins and occluding their ability to spread from cell-to-cell may be useful to provide novel treatments along with an in-depth knowledge of GBM neurobiology. Since these proteins appear to be regulated by the autophagy pathway, in the present study, we administered the gold standard mTOR inhibitor/autophagy inducer, rapamycin, to analyze the effects on GBM cell cultures concerning the expression of specific prionoids. Rapamycin dose- dependently suppresses the expression of prion-like proteins, while producing a marked differentiation of GBM cells. These effects are remarkable when transwell co-cultures of normal human astrocytes (NHA) are seeded in close contact with GBM cells separated by a semi-permeable membrane. In these experi- mental conditions, a transformation of astrocytes occurs along with increased expression of prionoids, which depends on the spreading of specific molecules through the membrane. Rapamycin administration occludes cell-to-cell spreading, while bringing back NHA to their previous phenotype
