Module 4
模組4
Physiological measures of
animal welfare (2):
動物福利之生理學測定法(二)
Neuroendocrine
神經內分泌系統
This module will enable you to
本模組的教學目標
• Understand the relationship between welfare
and physiology了解動物福利與生理學的關係
• Examine how the neuroendocrine system is
associated with welfare檢視神經內分泌系統與動
物福利之關係
• Understand how neuroendocrine responses
can be used to assess welfare了解如何利用神經
內分泌反應測量動物福利
• Identify some pros/cons of using
neuroendocrine measures to assess welfare
動物福利測量方法的正反理由
Review
複習模組3之內容
Change in welfare
動物福利改變
װ
Change in physical & psychological
states
生理及心理狀態改變
װ
Physiological responses
產生生理反應
Review
複習模組3之內容
Change in welfare
當動物福利改變時
Activation of CNS
中樞神經系統受刺激活化
Autonomic nervous
responses
Neuroendocrine
responses
自主神經系統反應
神經內分泌系統反應
Neuroendocrine system
關於神經內分泌系統
• A welfare change affects three subdivisions of the neuroendocrine system:
動物福利變化影響下列三個神經內分泌子系統：
– Hypothalamus 下視丘
– Pituitary gland 腦下垂體
– Adrenal gland 腎上腺
Hypothalamic-Pituitary-Adrenal
Axis (HPA)
下視丘-腦下垂體-腎上腺（HPA軸）
• Major mediator of endocrine responses內分泌反應
的主要媒介
• HPA increases mobilisation of energy stores for
physical response HPA加強動員儲存的能量，供生理
反應所需
• HPA mediates responses to: HPA調節的反應包括：
– Stress 壓力
─ Sexual activity 性行為
– Courtship 求偶 ─ Food arrival / foraging 尋覓食物
HPA cascade HPA軸作用流程
Hypothalamus 下視丘
腦下垂體前葉釋放激素
CRH
corticotrophin-releasing hormone
Anterior pituitary gland 腦下垂體前葉
促腎上腺皮質激素
ACTH adrenocorticotrophic hormone
Adrenal cortex 腎上腺皮質
糖皮質素
Glucocorticoids
Liver
Stimulus
刺激
肝臟
HAP vessels
下視丘前葉血管
Module 4
Circulation
血流
HPA characteristics
HPA軸之特性
• Response not as immediate as
sympathetic adreno-medullary system 反應
比交感腎上腺系統慢
• Measure of acute welfare changes 可測量
急性的動物福利變化
– For example, plasma glucocorticoids elevated
between 2-10 minutes after stimulation 動物在
受到刺激後2-10分鐘，糖皮質素的血中濃度提昇
– Can remain elevated for hours depending on
severity of stimulus 依照刺激的強弱，其濃度可以
在血中維持數小時
Glucocorticoid measurement
糖皮質素測量評估
Method
Invasive
Restrictive
Disturbing
方法
侵入性
限制性
干擾性
Plasma
or
or
血漿
Saliva
唾液
Urine
尿液
Faeces
糞便
Glucocorticoid measurement
糖皮質素測量評估
• Analytical methods 分析方法
– Enzyme-linked immunosorbent assay 酵素
連結免疫吸附分析
– High performance liquid chromatography
高壓液相層析分析
– Competitive protein binding assay 蛋白質結
合競爭分析
– Radioimmunoassay 同位素免疫分析
Glucocorticoids
糖皮質素
• Corticosterone: rodents, birds 囓齒、鳥類
• Cortisol: humans, pigs,
and monkeys 人類、豬、猴
• Useful direct measure
有用的直接測量準則
Glucocorticoid example 1
糖皮質素作用例1
• Cortisol in lambs in response to:
– Tail-docking 小羊在實施斷尾
手術時糖皮質素會升高
– Castration小羊在實施閹割手
術時糖皮質素會升高
(Mellor & Murray, 1989)
Glucocorticoid example 2
糖皮質素作用—例二
• Urinary cortisol increases in
domestic dogs if they are put in
kennels 家犬隻若是被關入狗舍中，可
在尿液中檢測到cortisol濃度上升
(Hennessey et al 1997)
• If the dog has not been in
kennels before, the increase is
greater than if the dog has
experienced kennels before 而且
沒有被關入狗舍經驗的犬隻反應更激烈，
濃度上升越多 (Hiby 2005)
Chronic welfare assessment
慢性福利反應評估
• Indirect assessment of HPA 間接HPA評估法
• Glucocorticoid receptors in the brain 腦中糖皮
質素受體數目
– Number of receptors decreased in rats that were
exposed to prolonged handling and disturbance 大
鼠在經歷重複保定、驚擾的刺激後，發現腦中的受體
數量減少 (Wadham, 1997)
• ACTH challenge test 促腎上腺皮質素測試
– ACTH is administered, and resulting glucocorticoid
levels measured 注射ACTH後測血液中糖皮質素量
ACTH challenge test
促腎上腺皮質素測試
• Example: Dairy cows
以乳牛飼養為例
– Long periods of overcrowding => higher
cortisol response than
if less crowded 經長期
密飼後血中cortisol會升高
(Friend et al., 1977)
Limitations to HPA measures
HPA測量技術之限制
Individual differences: 個體差異
– Early experience 早年生活經驗
(Levine et al., 1967)
– Sex 性別
(Livezey et al., 1985)
– Metabolism 代謝狀態
Limitations to HPA measures
HPA測量技術之限制（續）
•
Species 物種
– New World Monkeys 新世界猴
(Klostermann et al., 1986)
•
Time when sampled 採樣時間
– Circadian rhythm 日夜規律
Limitations to HPA measures
HPA測量技術之限制（續）
•
Disturbance due to measurement 測量
之干擾
•
Human presence, handling, restraint
and sampling method 有人在動物旁邊、人
觸摸動物、保定，甚至是採樣方式不當
Other autonomic measures of
animal welfare
其他測量動物福利之項目
• Body temperature 體溫
• Opioid levels 類鴉片物質濃度
• Organ pathology 器官病理變化
Body temperature
體溫代表的意義
• Acute welfare measure 急性的福利測量
• Changes in other physiological systems (e.g.
adrenal activity) => changes in core body
temperature 其他生理系統產生變化（如腎上腺活性改變）
造成中心體溫出現改變
• Rat body temperature by storms and unfamiliar
people 暴風與陌生人會使大鼠的體溫升高(Georgiev,
1978)
• body temperature in defeated tree shrews 社會
地位挑釁落敗的樹鼩體溫反而下降(von Holst, 1986)
Temperature measurement
體溫測量
Method
Site
方法
採樣位置
Core
Temp
中心體溫
Direct, e.g.
thermometer
直接法--體溫計
Telemetry
嵌入遙測裝置
Thermoimaging
體表溫度照影
Invasi Restrictive Disturbing
ve
限制性
干擾性
侵入
性
Mouth,口
ear 耳 &
rectal 肛
Internal
體內
+/-
+/-
Skin
皮膚
Opioids
類鴉片類物質
• Three types 3種型式
– Endorphins 腦內啡
– Enkephalins 腦啡肽
– Dynorphins 強啡肽
• Functions: 功能
– Stress-induced analgesia 調適緊迫的止痛劑
– Control hormone release控制激素之分泌
Opioid measurement
類鴉片類之測量
Method
Invasive Restrictive
Disturbing
方法
侵入性
干擾性
Blood
血液
Brain receptors
腦內受體
限制性
Opioid examples
類鴉片類作用之實例
• Increase in plasma ß-endorphin in
lambs during castration, tail docking and
mulesing 綿羊在受閹割、斷尾、切臀皮時，血中ß腦內啡量會增加(Shutt et al.,1987)
• Tethered sows had higher opioid
receptor density than group-housed
sows 繫頸鏈的豬比群飼豬有較高之類鴉片類受體密
度(Zanella et al., 1996)
Organ Pathology
器官病變
• Chronic welfare changes => wide variety of
pathologies 慢性動物福利變化可造成多處器官病變
• Most are measured post-mortem e.g., 大部分
是藉由死後解剖來觀察，例如：
– Adrenal hypertrophy 腎上腺肥大
– Kidney lesions 腎臟病變
– Myocardial lesions 心肌病變
• In vivo 活體觀察
– Stomach ulcers 胃潰瘍
Pathology examples
器官病變之例
• Social instability in female groups of rats =
adrenal hypertrophy 置身於不安定社會之雌性大鼠
出現腎上腺肥大的病變(Haller et al., 1999)
• Subordinate mice show kidney lesions in the
presence of dominant animals 在強勢小鼠之存
在下，弱勢鼠產生腎臟的病變 (Henry & StephensLarson, 1985)
• Myocardial lesions associated with longer
periods of restraint in pigs 豬受到長期保定與心肌
病變有關 (Wutzen et al., 1987)
Conclusion
總結與討論
• Neuroendocrine system => acute and chronic
measures of welfare 神經內分泌系統可作為動物福
利之急性與慢性測量
• Direct and indirect ANS measures中樞神經系統
反應有直接與間接之測量
• Limitations of measures神經內分泌系統之測量有
其限制，故評估時要小心
• Other physiological responses can also be
used to assess welfare e.g. temperature,
organ pathology, and opioid levels 其他生理學
之反應亦可用來評估動物福利，包括體溫、器官之病理
變化、與血中類鴉片類濃度
Further reading
進階閱讀
• FRIEND, T.H., POLAN, C.E., GWAZDAUSKAS, F.C. & HEALD,
C.W., 1977: Adrenal glucocorticoid response to exogenous
adrenocorticotrophin mediated by density and social disruption in
dairy cows. J. Diary Sci. 60, 1958-1963
• GEORGIEV J. 1978 Influence of environmental conditions and
handling on temperature rhythm of the rat. Biotelemetry Patient
Monit. 5, 229-234
• HALLER J, FUCHS E, HALASZ J & MAKARA GB. 1999 Defeat is a
major stressor in males while social instability is stressful mainly in
females: Towards the development of a social stress model in
female rats. Brain Research Bulletin 50 (1): 33-39
• HENNESSEY MB, DAVIS HN, WILLIAMS MT, MELLOTT C &
DOUGLAS CW 1997 Plasma cortisol levels of dogs at a county
animal shelter. Physiol Behav 62: 485-490
Further reading
進階閱讀
• HENRYJP & STEPHENS-LARSON P. 1985 Specific aspects of
stress on disease processes. In: MOBERG, G. P. (Ed.) Animal Stress.
American Physiological Association, Maryland, USA
• HIBY EF 2005 The Welfare of Kennelled Domestic Dogs. PhD Thesis,
University of Bristol
• KALIN NH, CARNES M, BARKSDALE CM, SHELTON SE,
STEWART RD & RISCH SC. 1985 Effects of acute behavioural
stress on plasma and cerebrospinal fluid, ACTH and -endorphin in
rhesus monkeys. Neuroendocrinology 40, 97-101
• KLOSTERMANN LL, MURAI JT & SIITERI PK. 1986 Cortisol levels,
binding and properties of corticosteroid-binding globulin in the serum
of primates. Endocrinology 118, 424-434
• LANG RE, HEIL JWE, GANTEN D, HERMANN K & UNGER T. 1983
Oxytocin, unlike vasopressin, is a stress hormone in the rat.
Neuroendocrinology 37, 314-316
Further reading
進階閱讀
• LANE J 2006 Can non-invasive glucocorticoid measures be used as
reliable indicators of stress in animals? Animal Welfare 15: 331-342
• LEVINE S, HALTMEYER GC, KARAS GG & DENENBERG VH. 1969
Physiological and behavioural effects of infantile stimulation.
Physiology and Behavior 2, 55-59
• LIVEZEY GT, MILLER JM & VOGEL WH. 1985 Plasma
norepinephrine, epinephrine and corticosterone stress responses to
restraint in individual male and female rats and their correlations.
Neurosci. Lett. 62, 51-56
• MELLOR DJ & MURRAY L. 1989 Effects of tail docking and
castration on behaviour and plasma cortisol concentrations in young
lambs. Res. Vet. Sci. 46, 387-391
Further reading
進階閱讀
• SHUTT, D.A., FELL, L.R., CONNELL, R., BELL, A.K., WALLACE,
C.A. & SMITH, A.I., 1987: Stress-induced changes in plasma
concentrations of immunosuppressive ß-endorphin and cortisol in
response to routine surgical procedures in lambs. Aust. J. Biol. Sci.
40, 97-103.
• VON HOLST D. 1986 Vegetative and somatic components of tree
shrews’ behaviour. J. Auton. Nerv. Syst. Suppl., 657-670
• WADHAM JJB. 1997 Recognition and reduction of adverse effects
in research on rodents. PhD Thesis, Faculty of Medicine and
Dentistry, The University of Birmingham
• WUTZEN J, LEWICKI Z, ROZYCKA Z, CEREMUZYNSKI L &
BARCIKOWSKI R. 1987 Effects of immobilisation stress on
histological, histochemical and electron-microscopic changes in
porcine myocardium. Mat. Med. Pol. 19, 78-84.
• ZANELLA AJ, BROOM DM, HUNTER JC, MENDL MT. 1996 Brain
opioid receptors in relation to stereotypies, inactivity, and housing in
sows. Physiol Behav 59: 769-775
