Leptin mediates protection of hydrogen sulfide against 6-hydroxydopamine-induced Parkinson's disease: Involving enhancement in Warburg effect

Identification of innovative therapeutic targets for the treatment of cognitive impairment in Parkinson’s disease (PD) is urgently needed. Hydrogen sulfide (H2S) plays an important role in cognitive function. Therefore, this work is aimed at investigating whether H2S attenuates the cognitive impairment in PD and the underlying mechanisms. In the rotenone- (ROT-) established PD rat model, NaHS (a donor of H2S) attenuated the cognitive impairment and promoted microglia polarization from M1 towards M2 in the hippocampus of PD rats. NaHS also dramatically upregulated the Warburg effect in the hippocampus of PD rats. 2-Deoxyglucose (2-DG, an inhibitor of the Warburg effect) abolished NaHS-upregulated Warburg effect in the hippocampus of PD rats. Moreover, the inhibited hippocampal Warburg effect by 2-DG abrogated H2S-excited the enhancement of hippocampal microglia M2 polarization and the improvement of cognitive function in ROT-exposed rats. Our data demonstrated that H2S inhibits the cognitive dysfunction in PD via promoting microglia M2 polarization by enhancement of hippocampal Warburg effect.

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Neuroprotective effect of Pioglitazone in the 6-hydroxydopamine model of Parkinson’s Disease

10.26226/morressier.5785edcfd462b80296c99fd3 ◽

2016 ◽

Author(s):

Maria Vital

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neuroprotective Effect ◽

6 Hydroxydopamine

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Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine

Scientific Reports ◽

10.1038/s41598-021-90094-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jui-Chih Chang ◽

Yi-Chun Chao ◽

Huei-Shin Chang ◽

Yu-Ling Wu ◽

Hui-Ju Chang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Olfactory Bulb ◽

Disease Model ◽

Intranasal Delivery ◽

The Difference ◽

And Migration ◽

6 Hydroxydopamine ◽

Locomotor Behaviors ◽

Migratory Stream

AbstractThe feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.

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A Guide to the Generation of a 6-Hydroxydopamine Mouse Model of Parkinson’s Disease for the Study of Non-Motor Symptoms

Biomedicines ◽

10.3390/biomedicines9060598 ◽

2021 ◽

Vol 9 (6) ◽

pp. 598

Author(s):

Débora Masini ◽

Carina Plewnia ◽

Maëlle Bertho ◽

Nicolas Scalbert ◽

Vittorio Caggiano ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mouse Model ◽

Survival Rates ◽

Dorsal Striatum ◽

Brain Regions ◽

Motor Symptoms ◽

Operative Care ◽

6 Hydroxydopamine ◽

Non Motor Symptoms

In Parkinson’s disease (PD), a large number of symptoms affecting the peripheral and central nervous system precede, develop in parallel to, the cardinal motor symptoms of the disease. The study of these conditions, which are often refractory to and may even be exacerbated by standard dopamine replacement therapies, relies on the availability of appropriate animal models. Previous work in rodents showed that injection of the neurotoxin 6-hydroxydopamine (6-OHDA) in discrete brain regions reproduces several non-motor comorbidities commonly associated with PD, including cognitive deficits, depression, anxiety, as well as disruption of olfactory discrimination and circadian rhythm. However, the use of 6-OHDA is frequently associated with significant post-surgical mortality. Here, we describe the generation of a mouse model of PD based on bilateral injection of 6-OHDA in the dorsal striatum. We show that the survival rates of males and females subjected to this lesion differ significantly, with a much higher mortality among males, and provide a protocol of enhanced pre- and post-operative care, which nearly eliminates animal loss. We also briefly discuss the utility of this model for the study of non-motor comorbidities of PD.

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