Adolescent ethanol drinking promotes hyperalgesia, neuroinflammation and serotonergic deficits in mice that persist into adulthood

Khan, Kanza; Rosa, Gabrielle Bierlein-De La; Biggerstaff, Natalie; Selvakumar, Govindhasamy Pushpavathi; Wang, Ruixiang; Mason, Suzanne; Dailey, Michael E.; Marcinkiewcz, Catherine A.

doi:10.1016/j.bbi.2022.07.160

Cited by 23 publications

(32 citation statements)

References 79 publications

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“…In addition to the inherent sex differences, our study showed that both male and female aCIE-exposed rats responded with paw withdrawal at a lower target force in the von Frey mechanical allodynia test. Our data concur with a recent study showing moderate ethanol exposure during early adolescence (PD 25 -53) mediated reduction in paw withdrawal threshold during protracted withdrawal in male mice [37].…”

Section: Discussionsupporting

confidence: 93%

“…Furthermore, in the current study, measurements of sensitivity to thermal nociception during protracted withdrawal revealed thermal hyperalgesia selectively in aCIE exposed male rats. In accordance with our data, a recent study reported attenuation in paw withdrawal latency in response to noxious thermal stimulus in male mice during protracted abstinence following adolescent ethanol exposure (PD 25 -53) [37]. Previous studies have also reported heightened thermal hyperalgesia during withdrawal from chronic ethanol exposure in adulthood in male rats [4,38].…”

Section: Discussionsupporting

confidence: 92%

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Adolescent ethanol exposure promotes mechanical allodynia and alters dopamine transmission in the nucleus accumbens shell

Kelley

Valle

Zaman

et al. 2022

Preprint

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Excessive alcohol consumption in adolescence can disrupt neural development and may augment pain perception. Recent studies have shown that the nucleus accumbens (NAc) shell is involved in mediating pain sensitivity after peripheral inflammation in rodent models of chronic pain and alcohol use disorder (AUD). Interestingly, there have been very few studies examining the impact of chronic ethanol exposure during adolescence on pain sensitivity in adulthood. Therefore, in this project we investigated the impact of adolescent chronic intermittent ethanol (aCIE) exposure on mechanical allodynia and thermal hyperalgesia. Furthermore, given the involvement of the NAc shell in pain processing and chronic ethanol mediated changes, we measured changes in accumbal dopamine kinetics during protracted withdrawal. We found that both male and female aCIE rats show mechanical allodynia during withdrawal; however, only male rats exhibit thermal hyperalgesia during protracted withdrawal. Furthermore, male and female aCIE rats show greater evoked tonic dopamine release, maximal rate of dopamine reuptake, and dopamine affinity to the dopamine transporter in the NAc shell compared to controls. With phasic stimulation, aCIE rats also showed greater dopamine release compared to air exposed rats. These data suggest that aCIE exposure exacerbates pain sensitivity during withdrawal. Furthermore, based on prior literature, it is possible that the increased pain sensitivity may be driven, at least in part, by augmented dopamine kinetics in the NAc shell observed in the current study.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Adolescent ethanol exposure promotes mechanical allodynia and alters dopamine transmission in the nucleus accumbens shell

Kelley

Valle

Zaman

et al. 2022

Preprint

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“…Although the stranger was confined to one chamber under the cage, it was clearly visible to the test animal. An empty cage was placed in the opposite-side chamber [33, 51]. Mice were allowed to roam freely between all chambers for another 10 minutes and interact with the stranger or empty cage.…”

Section: Methodsmentioning

confidence: 99%

“…Forced Swim: The forced swim assay was used to evaluate depressive-like behaviors following injection of AAV-P301L-tau in the DRN of male mice. A tall, clear cylinder was filled with 24-25⁰C tap water (32cm height x 20cm diameter; water height 25cm), and mice were gently placed inside for 6 minutes [33]. Following the test, mice were promptly removed from the cylinders and placed in a fresh, dry cage under a heat lamp for 5 minutes to allow them to warm up and dry off.…”

Section: Behavior Assaysmentioning

confidence: 99%

“…In females, all tests except the Barnes Maze and Forced Swim were performed. Elevated Plus Maze: Mice were placed in the center of an elevated, plus-shaped maze with open and enclosed arms (arms 35cm long, 5cm wide, 60cm off the ground; enclosed arms with 20cm high walls) and allowed to explore for five minutes as reported previously [33]. The assay was performed under dim light (~20 lux in open arms, and < 5 lux in closed arms) with the experimenter blocked from view using an opaque curtain.…”

Section: Behavior Assaysmentioning

confidence: 99%

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Tau pathology in the dorsal raphe may be a prodromal indicator of Alzheimer’s disease

Pierson

Fiock

Wang

et al. 2022

Preprint

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Protein aggregation in brainstem nuclei is thought to occur in the early stages of Alzheimer's disease (AD), but its specific role in driving prodromal symptoms and disease progression is largely unknown. The dorsal raphe nucleus (DRN) contains a large population of serotonin (5-hydroxytryptamine; 5-HT) neurons that regulate mood, reward-related behavior, and sleep, all of which are disrupted in AD. We report here that tau pathology is present in the DRN of cognitively intact individuals 54-80 years of age, whereas synuclein and TDP-43 are relatively absent. Almost all AD cases had tau pathology in the DRN, whereas only a subset contained TDP-43 or synuclein, but not both. Mice overexpressing human P301L-tau in the DRN also exhibited depressive-like behaviors and hyperactivity without any deficits in spatial memory. There was a negative correlation between the density of Tph2-expressing neurons and phospho-tau (ptau) optical density in P301L-tauDRNmice, although mean Tph2 expression did not differ significantly from the controls. 5-HT neurons were hyperexcitable in P301L-tauDRNmice, and there was an increase in the amplitude of excitatory post-synaptic currents (EPSCs) which is suggestive of increased glutamatergic transmission. Astrocytic density was also elevated in the DRN and accompanied by an increase in GFAP expression, as well as changes inHtr2a, Htr2c,andHtr3agene expression. Additionally, tau pathology was detected in axonal processes in the thalamus, hypothalamus, amygdala, and caudate putamen, suggesting that tau may spread in an anterograde manner to regions outside the DRN. Together, these results suggest that tau pathology accumulates in the DRN in a subset of individuals over 50 years and may lead to prodromal AD symptoms, 5-HT neuronal dysfunction, and activation of local astrocytes. The presence of tau pathology in the DRN combined with psychiatric assessments for depression may be a useful screening tool for individuals at risk for AD.

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Chemogenetic modulation of astrocytes and microglia: State‐of‐the‐art and implications in neuroscience

Bossuyt

Herrewegen

Nestor

et al. 2023

Glia

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Insights into the role astrocytes and microglia play in normal and diseased brain functioning has expanded drastically over the last decade. Recently, chemogenetic tools have emerged as cutting-edge techniques, allowing targeted and spatiotemporal precise manipulation of a specific glial cell type. As a result, significant advances in astrocyte and microglial cell function have been made, showing how glial cells can intervene in central nervous system (CNS) functions such as cognition, reward and feeding behavior in addition to their established contribution in brain diseases, pain, and CNS inflammation. Here, we discuss the latest insights in glial functions in health and disease that have been made through the application of chemogenetics. We will focus on the manipulation of intracellular signaling pathways induced by activation of the designer receptors exclusively activated by designer drugs (DREADDs) in astrocytes and microglia. We will also elaborate on some of the potential pitfalls and the translational potential of the DREADD technology.

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Adolescent ethanol drinking promotes hyperalgesia, neuroinflammation and serotonergic deficits in mice that persist into adulthood

Cited by 23 publications

References 79 publications

Adolescent ethanol exposure promotes mechanical allodynia and alters dopamine transmission in the nucleus accumbens shell

Adolescent ethanol exposure promotes mechanical allodynia and alters dopamine transmission in the nucleus accumbens shell

Tau pathology in the dorsal raphe may be a prodromal indicator of Alzheimer’s disease

Chemogenetic modulation of astrocytes and microglia: State‐of‐the‐art and implications in neuroscience

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