Quantification of brainstem norepinephrine relative to vocal impairment and anxiety in the Pink1-/- rat model of Parkinson disease

Hoffmeister, Jesse D.; Kelm‐Nelson, Cynthia A.; Ciucci, Michelle R.

doi:10.1016/j.bbr.2021.113514

Cited by 20 publications

(17 citation statements)

References 112 publications

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“…Locus Coeruleus: Tyrosine hydroxylase (TH), the enzyme catalyzing the rate-limiting step in catecholamine biosynthesis, is frequently used in the immunohistochemical identification of noradrenergic LC neurons [ 30 , 32 ] and is even considered a noradrenergic marker of the LC [ 31 ]. It was, therefore, used here to study the LC.…”

Section: Resultsmentioning

confidence: 99%

“…The increase in the levels of the enzyme TH, frequently used as a validated method to identify noradrenergic LC neurons [ 30 , 31 ], has never been reported in the kaolin-induced hydrocephalus model. To perform a correct counting of the TH-IR neurons in the LC, a specific processing of brainstem tissue should be performed to allow precise morphometric analysis, such as the stereological technique [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…The increases in TH at the LC of hydrocephalus rats may be explained by the high levels of oxidative stress detected in local neurons. Due to the obstruction of the connection between the ventricular system and the intracranial and subarachnoidal space and obstruction of CSF circulation [ 4 , 30 , 31 , 40 ], some brain areas may be hypoxic. In hypoxic situations, there is an increase in the number of reactive oxygen species (ROS) leading to an oxidative imbalance and consequently to a state of oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, local changes in NA expression affect top–down pain modulation [ 28 ], and oxidative stress is a problem in hydrocephalic patients [ 29 ]. These questions were evaluated using a validated kaolin-induced hydrocephalus model, causing ventricular and aqueductal enlargement due to oxidative stress-mediated inflammatory reaction of the circumventricular tissue [ 4 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

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Pain Modulation from the Locus Coeruleus in a Model of Hydrocephalus: Searching for Oxidative Stress-Induced Noradrenergic Neuroprotection

Louçano

Oliveira

Martins

et al. 2022

IJMS

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Pain transmission at the spinal cord is modulated by noradrenaline (NA)-mediated actions that arise from supraspinal areas. We studied the locus coeruleus (LC) to evaluate the expression of the cathecolamine-synthetizing enzyme tyrosine hydroxylase (TH) and search for local oxidative stress and possible consequences in descending pain modulation in a model of hydrocephalus, a disease characterized by enlargement of the cerebral ventricular system usually due to the obstruction of cerebrospinal fluid flow. Four weeks after kaolin injection into the cisterna magna, immunodetection of the catecholamine-synthetizing enzymes TH and dopamine-β-hydroxylase (DBH) was performed in the LC and spinal cord. Colocalization of the oxidative stress marker 8-OHdG (8-hydroxyguanosine; 8-OHdG), with TH in the LC was performed. Formalin was injected in the hindpaw both for behavioral nociceptive evaluation and the immunodetection of Fos expression in the spinal cord. Hydrocephalic rats presented with a higher expression of TH at the LC, of TH and DBH at the spinal dorsal horn along with decreased nociceptive behavioral responses in the second (inflammatory) phase of the formalin test, and formalin-evoked Fos expression at the spinal dorsal horn. The expression of 8-OHdG was increased in the LC neurons, with higher co-localization in TH-immunoreactive neurons. Collectively, the results indicate increased noradrenergic expression at the LC during hydrocephalus. The strong oxidative stress damage at the LC neurons may lead to local neuroprotective-mediated increases in NA levels. The increased expression of catecholamine-synthetizing enzymes along with the decreased nociception-induced neuronal activation of dorsal horn neurons and behavioral pain signs may indicate that hydrocephalus is associated with alterations in descending pain modulation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pain Modulation from the Locus Coeruleus in a Model of Hydrocephalus: Searching for Oxidative Stress-Induced Noradrenergic Neuroprotection

Louçano

Oliveira

Martins

et al. 2022

IJMS

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“…Finally, Pink1 -/- rats display behavioral deficits in motor and non-motor functions that mimic those experienced by PD patients. For example, in addition to age-related decline in gait coordination and grip strength(Dave, De Silva et al 2014), Pink1 -/- rats also demonstrate early-appearing deficits in sensorimotor cranial/otolaryngeal functions that negatively impact vocalizations, chewing and swallowing (Grant, Kelm-Nelson et al 2015, Cullen, Grant et al 2018, Kelm-Nelson, Brauer et al 2018, Kelm-Nelson, Lechner et al 2021). In addition, Pink1 -/- rats also show behavioral correlates reflecting increased anxiety, e.g., changes in distress vocalizations, social approach, open vs. closed arm entries in elevated plus maze testing (Kelm-Nelson, Brauer et al 2018, Cai, Qiao et al 2019, Hoffmeister, Kelm-Nelson et al 2021, Hoffmeister, Kelm-Nelson et al 2022).…”

Section: Introductionmentioning

confidence: 99%

Spontaneous object exploration in a recessive gene knockout model of Parkinson’s disease: Development and progression of object recognition memory deficits in male Pink1-/- rats

Pinizzotto

Dreyer

Aje

et al. 2022

Preprint

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Cognitive impairments appear at or before motor signs in about one third of patients with Parkinson’s disease (PD) and have a cumulative prevalence of roughly 80% overall. These deficits exact an unrelenting toll on patients’ quality and activities of daily life due in part to a lack of available treatments to ameliorate them. This study used three well-validated novel object recognition-based paradigms to explore the suitability of rats with knockout of the PTEN-induced putative kinase1 gene (Pink1) for investigating factors that induce cognitive decline in PD and for testing new ways to mitigate them. Longitudinal testing of rats from three to nine months of age revealed significant impairments in male Pink1-/- rats compared to wild type controls in Novel Object Recognition, Novel Object Location and Object-in-Place tasks. Task-specific differences in the progression of object discrimination/memory deficits across age were also seen. Finally, testing using an elevated plus maze, a tapered balance beam and a grip strength gauge showed that in all cases recognition memory deficits preceded potentially confounding impacts of gene knockout on affect or motor function. Taken together, these findings suggest that knockout of the Pink1 gene negatively impacts the brain circuits and/or neurochemical systems that support performance in object recognition tasks. Further investigations using Pink1-/-rats and object recognition memory tasks should provide new insights into the neural underpinnings of the visual recognition memory and visuospatial information processing deficits that are often seen in PD patients and accelerate the pace of discovery of better ways to treat them.

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Pink1-/- Rats Demonstrate Swallowing and Gastrointestinal Dysfunction in a Model of Prodromal Parkinson Disease

et al. 2023

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Quantification of brainstem norepinephrine relative to vocal impairment and anxiety in the Pink1-/- rat model of Parkinson disease

Cited by 20 publications

References 112 publications

Pain Modulation from the Locus Coeruleus in a Model of Hydrocephalus: Searching for Oxidative Stress-Induced Noradrenergic Neuroprotection

Pain Modulation from the Locus Coeruleus in a Model of Hydrocephalus: Searching for Oxidative Stress-Induced Noradrenergic Neuroprotection

Spontaneous object exploration in a recessive gene knockout model of Parkinson’s disease: Development and progression of object recognition memory deficits in male Pink1-/- rats

Pink1-/- Rats Demonstrate Swallowing and Gastrointestinal Dysfunction in a Model of Prodromal Parkinson Disease

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