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Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting millions of people worldwide. At present, there is no effective cure for PD; treatments are symptomatic and do not halt progression of neurodegeneration. Extracellular vesicles (EVs) can cross the blood–brain barrier and represent promising alternative to the classical treatment strategies. In the present study, we examined therapeutic effects of intranasal administration of EVs derived from human exfoliated deciduous teeth stem cells (SHEDs) on unilateral 6‐hydroxydopamine (6‐OHDA) medial forebrain bundle (MFB) rat model of PD. CatWalk gait tests revealed that EVs effectively suppressed 6‐OHDA‐induced gait impairments. All tested gait parameters (stand, stride length, step cycle, and duty cycle) were significantly improved in EV‐treated animals when compared with 6‐OHDA‐lesion group rats. Furthermore, EVs slowed down numbers of 6‐OHDA‐induced contralateral rotations in apomorphine test. Improvements in motor function correlated with normalization of tyrosine hydroxylase expression in the striatum and substantia nigra. In conclusion, we demonstrated, for the first time, the therapeutic efficacy of intranasal administration of EVs derived from SHEDs in a rat model of PD induced by 6‐OHDA intra‐MFB lesion. Our findings could be potentially exploited for the development of new treatment strategies against PD.

Members of the solute carrier families (SLC) 32, 36, and 38, together also designated the beta-group of SLCs, are known to transport neutral amino acids. In this paper, we show that these three families were present before the split of the animal lineage and that they are likely to share a common decent. We also show that the APF transporters found in plants are most likely homologous to the mammalian beta-group, suggesting that this type of transporters arouse early in the evolution of eukaryotes. We performed detailed tissue expression analysis of all the members of the beta-group in rat and found several examples of highly specific expression patterns, with SLC38A7 being exclusively found in liver, SLC38A5 in blood, and SLC38A4 in muscle and liver. Moreover, we found that SLC38A10 is expressed in several endocrine organs. We also found that SLC38A1 is highly up regulated in the cortex from rats treated with diazepam and that SLC38A2 is significantly down regulated in the same tissue. In addition, we performed a detailed expression analysis of SLC38A1 and SLC38A6 in mouse brain using in situ hybridization, which showed that both these transporters are widely expressed in the brain.

Strong evidence suggests a functional link between the melanocortin and dopamine systems. alpha-Melanocyte stimulating hormone (alpha-MSH) induced grooming behaviour, which can be blocked by dopamine receptor antagonists, is associated with increased dopaminergic transmission in the striatal regions. Whether this effect is mediated specifically by melanocortin (MC) receptors has not previously been established. Using in vivo microdialysis on anesthesized rats we have shown that alpha- MSH administered into the ventral tegmental area induced a significant increase in dopamine and DOPAC levels in the nucleus accumbens. This increase was completely blocked by pre-treatment with the MC4 receptor selective antagonist HS131, indicating that the effects of alpha-MSH on dopamine transmission may be mediated by the MC4 receptor.

Effects of a Hypericum extract in therapeutic use and hyperforin sodium salt were evaluated in rat and mouse avoidance tests. In a conditioned avoidance response (CAR) test on the rat, oral daily administration of hyperforin (1.25 mg/kg/day) or of the extract (50 mg/kg/day) before the training sessions considerably improved learning ability from the second day onwards until the day 7. In addition, the memory of the learned responses acquired during 7 consecutive days of administration and training was largely retained even after 9 days without further treatment or training. The observations made using different doses indicate that these learning-facilitating and/or memory-consolidating effects by the agents follow inverse U-shaped dose-response curves in dose ranges lower than (for hyperforin) or equal to (for Hypericum extract) their effective dose in the behavioral despair test for antidepressants. In a passive avoidance response test on the mouse, a single oral dose (1.25 mg/kg) of hyperforin not only improved memory acquisition and consolidation, but also almost completely reversed scopolamine-induced amnesia. The single Hypericum extract dose tested (25 mg/kg) did not reveal any significant effects in the passive avoidance response (PAR) test on the mouse. These observations suggest that the Hypericum extract could be a novel type of antidepressant with memory enhancing properties, and indicate that hyperforin is involved in its cognitive effects. Pure hyperforin seems to be a more potent antidementia agent than an antidepressant.

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